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ME-CFS

SAMHD1 Research Digest — 2026-07-05

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 8 papers evaluated | 4 high-relevance (≥7) | 3 medium (5–6) | 1 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Early brain-penetrant immunotherapy reverses interferon signature and improves motor outcome in a case of ADAR1-related Aicardi-Goutières syndrome. (from Pediatric Neurology / Neuroimmunology)
Dale Russell C; Hayes Jessica; Han Velda X; Dissanayake Ruwani; Lau Xianzhong — 2026
Score: 8/10 | Pathways: cGAS-STING, JAK-STAT, ISG15-mitophagy, AGS-spectrum, treatment-target, clinical-phenotype

This paper directly demonstrates reversal of the type I interferon signature (including downregulation of CGAS, SAMHD1, ISG15, and JAK1) by ruxolitinib + dexamethasone in an AGS interferonopathy, with single-cell RNA-seq validating the same core molecular players central to the SAMHD1 A565T disease mechanism, and provides a clinically actionable brain-penetrant JAK-inhibitor treatment precedent directly applicable to the interferon-driven neurodevelopmental and ME/CFS phenotypes in this family.
DOI: 10.1002/cti2.70113

JAK Inhibition in <i>PNPT1</i>-Related Mitochondrial Interferonopathy: A Case Report and Review of Mitochondrial-Immune Crosstalk. (from Pediatric neurology / mitochondrial medicine)
Brooks Dan Ross; Koh Hyun Yong; Kerrins Taylor Martin; Lang Steven; Bland Emily — 2026
Score: 8/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, POLG-mtDNA, ISG15-mitophagy, treatment-target, clinical-phenotype

This case report directly demonstrates JAK inhibitor (tofacitinib) efficacy in a mitochondrial interferonopathy caused by mt-dsRNA cytosolic leakage activating IFN-I signaling—mechanistically parallel to the SAMHD1 A565T pathway where VDAC1 macropore releases mtDNA to activate cGAS-STING-IRF3-IFN-I-JAK-STAT, and provides clinical proof-of-concept that JAK inhibition can normalize IFN signature and downstream pathology (dystonia, lactate, transaminases) in mitochondrial-immune crosstalk syndromes including AGS-spectrum disease.
DOI: 10.1002/jmd2.70096

Aicardi-Goutières Syndrome: Insights from a Middle Eastern Case Series. (from Pediatric Neurology / Neuroradiology)
Alwalid Osamah; Al Subhi Marwa; Al Serhan Ala Aldeen; Abdulwahhab Saja B; Samran — 2026
Score: 7/10 | Pathways: AGS-spectrum, dNTPase, cGAS-STING, clinical-phenotype, JAK-STAT

This case series directly characterizes SAMHD1-associated AGS in a clinical cohort, including two siblings with a homozygous SAMHD1 variant presenting with chronic arthritis but no neurological disease—a phenotype highly relevant to understanding the genotype-phenotype spectrum of SAMHD1 variants and validating the arthritis/interferonopathy axis central to the family phenotype described.
DOI: 10.3174/ajnr.a9239

SLC30A9-mediated mitochondrial zinc homeostasis drives osteosarcoma chemoresistance by suppressing the mtDNA-cGAS-STING pathway. (from Oncology (osteosarcoma/cancer biology))
Li Hongyu; Yang Biao; Liu Yinliang; Yang Wen; Yu Haoye — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper mechanistically demonstrates that mitochondrial dysfunction → mtDNA cytosolic release via mPTP opening → cGAS-STING activation, directly paralleling the BLUE stream (VDAC1/mtDNA/cGAS-STING axis) central to SAMHD1 haploinsufficiency pathology, and introduces a novel upstream regulator (mitochondrial zinc homeostasis via SLC30A9) of this pathway with therapeutic implications, though the context is osteosarcoma chemoresistance rather than interferonopathy.
DOI: 10.1016/j.lfs.2026.124555

🟡 Medium Relevance (Score 5–6)

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Myeloid STING restrains cardiac remodeling by suppressing macrophage amyloid precursor protein (from Cardiology)
Natarajan Niranjana; Johny Ebin; Sriram Varsha; Hara Mika; Antwi Praise Ama — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, other

This paper directly demonstrates mtDNA release activating cGAS-STING in cardiac macrophages and reveals a cardioprotective STING-MZF1-APP axis, which is mechanistically adjacent to the BLUE stream (VDAC1→mtDNA→cGAS→STING→IRF3) and relevant to the cardiology phenotype dimension of the disease profile, though the STING function here is tissue-protective rather than interferonopathic and SAMHD1 is not mentioned.
DOI: 10.64898/2026.07.01.735895

Daphnetin alleviates influenza pneumonia by enhancing chaperone-mediated autophagy of KEAP1 through Heat shock cognate 71 kDa protein. (from Pulmonology / natural product pharmacology)
Wang Jian; Liu Huan; Pan Xuanhao; Liu Tianyu; Li Qianyuan — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, mTOR-lysosomal, treatment-target, ME-CFS, other

This paper directly demonstrates that mtDNA leakage activates cGAS-STING inflammation in macrophages during viral pneumonia, and describes a therapeutic axis (HSC70-CMA-NRF2) that mitigates mitochondrial oxidative stress and mtDNA escape—mechanistically adjacent to the BLUE and RED streams of the SAMHD1 interferonopathy model—with potential relevance to the post-viral (ME/CFS) and cGAS-STING-driven IFN-I amplification loops, though SAMHD1, VDAC1, NLRP3, ISG15, or dNTP biology are not addressed.
DOI: 10.1016/j.phymed.2026.158517

Gut Microbiota-Derived TMAO Drives MC3T3-E1 Senescence and Osteogenic Dysfunction via cGAS-STING-NF-κB Signaling: Implications for Age-Related Bone Loss. (from Bone biology / osteoporosis / geriatrics)
Li Lingling; Li Xinsai; Jin Mingming; Zhang Yangyang; Bai Jia — 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, other

This paper demonstrates that mtDNA cytosolic escape activates cGAS-STING-NF-κB to drive cellular senescence, directly implicating the BLUE-stream mechanism central to SAMHD1 haploinsufficiency pathology, but in an osteoblast/bone-loss context with no connection to SAMHD1, interferonopathy, or the family's specific phenotypes.
DOI: 10.1007/s00223-026-01567-x

🟢 Low Relevance (Score 3–4)

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The mitochondrial protease, LonP1, is a potential cardioprotective target for attenuating doxorubicin-induced cardiomyocyte death. (from Cardiology/Oncology)
O'Dwyer Kienan P; Bauer Perry E; Dziadowicz Sebastian A; Pal Subhankhi; Eminhize — 2026
Score: 4/10 | Pathways: POLG-mtDNA, cGAS-STING, VDAC1, clinical-phenotype, other

This paper addresses mtDNA release from damaged mitochondria activating inflammatory and apoptotic signaling (relevant to the BLUE/PURPLE streams via cytosolic mtDNA → cGAS-STING and VDAC1 macropore concepts), but the context is doxorubicin cardiotoxicity and LonP1 protease biology rather than SAMHD1 haploinsufficiency, interferonopathy, or any core family pathway, making the connection tangential despite mechanistic overlap in mtDNA leakage.
DOI: 10.1186/s12967-026-08537-9

Pathway Coverage This Week

  • cGAS-STING: 8 papers
  • POLG-mtDNA: 6 papers
  • other: 5 papers
  • treatment-target: 4 papers
  • clinical-phenotype: 4 papers
  • VDAC1: 4 papers
  • JAK-STAT: 3 papers
  • AGS-spectrum: 3 papers
  • ISG15-mitophagy: 2 papers
  • dNTPase: 1 papers
  • mTOR-lysosomal: 1 papers
  • ME-CFS: 1 papers

SAMHD1 Research Digest — 2026-06-28

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 12 papers evaluated | 6 high-relevance (≥7) | 5 medium (5–6) | 1 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Fibroblast Mitochondrial Ca2+ Overload Drives Skin Fibrosis via mtDNA Leakage and cGAS-STING Activation in Systemic Sclerosis. (from Rheumatology/connective tissue disease (systemic sclerosis))
Zhang Xiaoyun; Wang Yingyu; Huang Hai; Guo Xinyi; Ye Wenjing — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the VDAC1 oligomerization → cytosolic mtDNA leakage → cGAS-STING activation axis in a fibrotic disease context, mechanistically validating the BLUE stream of the SAMHD1 haploinsufficiency model, and identifies VDAC1 inhibition and STING inhibition (H-151) as therapeutic targets with in vivo efficacy—highly actionable for the treatment-target framework.
DOI: 10.1002/art.70261

Delphinidin targets voltage-dependent anion channel 1 to inhibit ferroptosis and protect against retinal photochemical damage. (from Ophthalmology/retinal biology)
Wang Hansheng; Li Keyi; Pu Haomou; Xiong Yaoyao; Luo Dan — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target

This paper directly demonstrates the VDAC1 oligomerization → cytosolic mtDNA leakage → cGAS-STING activation axis that is central to the BLUE stream of the disease mechanism, and identifies delphinidin as a direct VDAC1-targeting compound that interrupts this cascade, making it highly relevant as both a mechanistic validation and a potential therapeutic lead analogous to VBIT-4.
DOI: 10.1016/j.phymed.2026.158455

Interrupting a mitochondrial DNA-driven innate immune circuit attenuates hepatic tissue remodeling and fibrotic architecture in experimental steatohepatitis. (from Hepatology)
Hamad Rabab S; Mohammed Sura Akram; Hasan Waseem Ali; AbuoHashish Norhan Ahmed; * — 2026
Score: 8/10* | Pathways: cGAS-STING, NLRP3, ISG15-mitophagy, IRF7-metabolic, POLG-mtDNA, treatment-target, clinical-phenotype

This paper directly interrogates the mtDNA-cGAS-STING-IRF3-IFN-β axis combined with NLRP3/IL-1β inflammasome and mitophagy (PINK1/Parkin) blockade in a metabolic liver disease model—mapping precisely onto the BLUE, RED, and PURPLE mechanistic streams of the SAMHD1 A565T interferonopathy, and demonstrating that dual upstream (mitophagy enhancement via urolithin A) plus downstream (STING inhibition via C176) targeting produces synergistic multi-domain control, providing directly translatable therapeutic logic for the hepatic steatosis phenotype documented in the family.
DOI: 10.1016/j.tice.2026.103733

Mitochondria-associated endoplasmic reticulum membrane (MAM): roles in innate immunity dysregulation. (from Cell biology / organelle biology)
Zhang Qingqi; Gao Junyan; Yang Yiting; Guo Ping; Gao Huiqin — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, treatment-target

This review directly covers the MAM as a hub integrating cGAS-STING activation, NLRP3 inflammasome, mtDNA release via mitochondrial fission/fusion dynamics, and mitophagy/autophagy flux—all four core pathways (PURPLE, BLUE, RED, GOLD) of the SAMHD1 A565T disease mechanism—and explicitly identifies the self-reinforcing cycle between MAM dysfunction and innate immune overactivation that underlies the proposed interferonopathy, making it highly mechanistically relevant even without direct SAMHD1 mention.
DOI: 10.1186/s12964-026-03013-9

Suppression of STING by Acacetin attenuates renal fibrosis via balancing mitophagy and protective nucleoid-phagy. (from Nephrology/Traditional Chinese Medicine pharmacology)
Gao Yujiu; Mu Linjie; Liu Chen; Zhao Yue; Cai Rui — 2026
Score: 7/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, treatment-target, mTOR-lysosomal

This paper directly investigates STING inhibition restoring mitophagy flux and mitochondrial quality control in a fibrotic context, directly relevant to the BLUE and RED pathway loops where cGAS-STING activation and mitophagy blockade drive the interferonopathy cycle in SAMHD1 haploinsufficiency; Acacetin's direct STING binding (Kd=1.57µM) and restoration of autophagic/mitophagic flux represent a novel small-molecule treatment-target insight.
DOI: 10.1016/j.jep.2026.122094

A negative regulator of mitochondrial complex I assembly adapts respiration to cellular energy demand. (from Mitochondrial cell biology / bioenergetics)
Li Zhirong; Chen Nuo; Zhou Caixia; Xu Lingna; Wang Xiyuan — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, other

TMEM141 regulates Complex I assembly and its deficiency causes oxidative mtDNA damage and mtDNA release activating cGAS-STING, directly engaging the BLUE stream of the disease mechanism where cytosolic mtDNA fragments drive cGAS→STING→IRF3→IFN-I, while the Complex I/OXPHOS connection links to the mitochondrial dysfunction central to the PURPLE and RED streams, offering a novel regulatory node (TMEM141/TIMMDC1/AFG3L2/YME1L1 axis) upstream of mtDNA escape.
DOI: 10.1016/j.molcel.2026.06.018

🟡 Medium Relevance (Score 5–6)

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Role and mechanism of nitric oxide-regulated cGAS/STING pathway-mediated inflammatory response in hypoglycemia-induced coronary artery endothelial cell injury. (from Cardiology/Endocrinology)
Luo Wenping; Wei Xiao; Xiao Qian — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, clinical-phenotype, treatment-target

This paper demonstrates a mechanistic link between mitochondrial damage, mtDNA release, and cGAS/STING pathway activation in coronary endothelial cells—directly overlapping with the BLUE and PURPLE streams of the SAMHD1 haploinsufficiency model—and validates STING inhibition as a cardioprotective strategy, which is relevant to the cardiology clinical context of the family phenotype.
DOI: 10.1371/journal.pone.0350983

cGAS-STING Pathway Mediates Retinal Pigmental Epithelial Dysfunction in Diabetic Retinopathy. (from Ophthalmology/Retinal medicine)
Zhu Zhaoqi; Qiu Aowang; Wang Ningyu; Zhu Ziyu; Yin Wenjie — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target

This paper directly demonstrates the mechanistic link between mitochondrial DNA leakage, cGAS-STING pathway activation, and downstream inflammation in a non-immune tissue context, validating the BLUE stream mechanism (mtDNA → cGAS → STING → inflammation) and showing STING inhibition as a pharmacological strategy, which is highly relevant to the core interferonopathy mechanism of SAMHD1 haploinsufficiency, though the disease context (diabetic retinopathy) is not directly related to the family phenotype.
DOI: 10.2337/db25-0128

GPAM mediates mitochondrial dysfunction and the progression of alcoholic liver disease through lipid remodeling. (from Hepatology)
Zhan Zibin; Liu Xuewen; Li Zehua; Qiao Xueyan; Li Shuo — 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, NLRP3, clinical-phenotype

This paper directly demonstrates that ceramide accumulation and cardiolipin loss disrupt mitochondrial dynamics and impair mitophagy, releasing mitochondrial DNA that activates cGAS-STING-driven inflammation—mechanistically mirroring the BLUE and RED pathway streams in SAMHD1 haploinsufficiency, and invoking ceramide (a named molecular player) alongside impaired mitophagy, though the context is alcoholic liver disease rather than interferonopathy.
DOI: 10.1126/sciadv.aef1896

Neuronal YTHDF2 suppresses innate immune activation in Aβ pathology by promoting m<sup>6</sup>A-dependent decay of cytosolic mitochondrial mRNAs. (from Neuroscience/Alzheimer's disease research)
Pan Wenqi; Yang Lin; Zhang Yao; Chen Yan; Xu Yuesi — 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, ME-CFS, AGS-spectrum, other

This paper describes cytosolic mitochondrial RNA fragments activating innate immune signaling (RIG-I-MAVS → IFN-β → JAK-STAT neuroinflammation), a parallel mechanism to the VDAC1/cGAS-STING axis in the disease profile where cytosolic mt-derived nucleic acids drive type I interferon responses, reinforcing the concept that mitochondrial nucleic acid escape is a convergent driver of interferonopathy relevant to the SAMHD1 syndrome's neurological and inflammatory phenotypes.
DOI: 10.1126/sciadv.adz0887

RBM10 Deficiency Promotes Anti-PD-1 Resistance in LUAD via STING Alternative Splicing-Driven CCL7 Signaling and Macrophage Polarization. (from Oncology/thoracic)
Gao Weitong; Wang Ruqiong; An Bo; Qi Lishuang; Jing Zihan — 2026
Score: 5/10 | Pathways: cGAS-STING, other

This paper identifies a STING alternative splicing mechanism (exon 3 exclusion) that modulates cGAS-STING signaling output and feeds into a mtDNA-cGAS-STING positive feedback loop via mitochondrial transfer, which is adjacent to the BLUE and PURPLE streams of the SAMHD1 A565T disease mechanism, but the context is lung adenocarcinoma immunotherapy resistance rather than interferonopathy or SAMHD1 haploinsufficiency.
DOI: 10.1002/advs.202522159

🟢 Low Relevance (Score 3–4)

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The transcription factor IRF8 drives tumor-specific exhaustion in CD8+ T cells. (from Oncology/Tumor Immunology)
Ongaro Marco; Thouenon Romane; Crespo Isaac; Dumez Alexandre; Charmoy Mélanie — 2026
Score: 3/10 | Pathways: JAK-STAT, other

The paper identifies IRF8 as a tumor-specific regulator of CD8+ T cell exhaustion suppressed by sustained IFN-I signaling, which has indirect relevance to the SAMHD1 disease context via the JAK-STAT/IFN-I axis, but does not engage any core pathways (cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, dNTPase) and focuses on tumor immunology rather than interferonopathy, mitochondrial dysfunction, or the family phenotypes described.
DOI: 10.1084/jem.20252115

Pathway Coverage This Week

  • cGAS-STING: 11 papers
  • VDAC1: 8 papers
  • POLG-mtDNA: 7 papers
  • treatment-target: 7 papers
  • other: 5 papers
  • ISG15-mitophagy: 4 papers
  • NLRP3: 3 papers
  • clinical-phenotype: 3 papers
  • JAK-STAT: 2 papers
  • IRF7-metabolic: 1 papers
  • mTOR-lysosomal: 1 papers
  • ME-CFS: 1 papers
  • AGS-spectrum: 1 papers

SAMHD1 Research Digest — 2026-06-21

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 27 papers evaluated | 12 high-relevance (≥7) | 9 medium (5–6) | 6 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Nucleotide metabolism reprogramming in obesity-associated cardiovascular inflammation: a new perspective (from Cardiology/Immunometabolism)
Taoming Qian; Mei Zhang; Yuhan Liu; Donghao Guo; Juan Jin — Frontiers in Immunology 2026
Score: 9/10 | Pathways: dNTPase, NLRP3, POLG-mtDNA, VDAC1, urate-NLRP3, treatment-target, clinical-phenotype, other

This paper directly models the SAMHD1→dNTP accumulation→mitochondrial dNTP import (SLC25/PNC transporters)→mtDNA oxidation→NLRP3 hyperactivation axis that is the core PURPLE and GOLD mechanism of the disease profile, demonstrating it in a cardiovascular/macrophage context with therapeutic node identification, making it highly mechanistically relevant even without the specific A565T variant.
DOI: 10.3389/fimmu.2026.1829718

The leaked mitochondrial DNA activated the cGAS-STING signaling pathway and exacerbated the motor dysfunction in mice caused by MPTP. (from Neurology/movement disorders)
Zhu Guangyao; Yu Xuanjie; Guo Yi; Yang Liting; Yang Qianhui — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the BLUE stream mechanism central to the disease model: mitochondrial stress → mtDNA leakage into cytosol → cGAS-STING activation → neuroinflammation, and validates STING inhibition as a therapeutic target, with direct relevance to the SAMHD1/VDAC1-mtDNA escape axis even though SAMHD1 is not mentioned.
DOI: 10.1016/j.expneurol.2026.115876

STING-OPTN signaling confers cytoprotection through TBK1-dependent mitophagy. (from Cell biology / mitochondrial quality control)
Zebo Huang; Jin-Yi Lin; Ling-Jun Cheng; Yong Wu; Xiangzheng Gao — Cell reports 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, POLG-mtDNA, mTOR-lysosomal, treatment-target

This paper directly implicates the cGAS-STING pathway as an upstream regulator of mitophagy via TBK1-OPTN signaling, which is mechanistically central to the BLUE and RED streams of the disease model—where constitutive STING activation from VDAC1/mtDNA escape not only drives IFN-I but also perturbs mitochondrial quality control, and the STING-OPTN mitophagy axis disruption switches cells toward apoptosis, directly mirroring the double mitophagy block (ISGylation of MFN1/2 and BECN1) and the apoptosis-autophagy switch (BIK/BH3) predicted in the family's pathomechanism.
DOI: 10.1016/j.celrep.2026.117515

STING1 senses mitochondrial damage to promote mitophagy. (from Cell biology / autophagy)
Zebo Huang; Jin-Yi Lin; Ling-Jun Cheng; H. Tan; Hanming Shen — Autophagy 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, POLG-mtDNA, ME-CFS, treatment-target

This paper directly demonstrates that STING1 acts as a non-canonical upstream regulator of PINK1/Parkin-dependent mitophagy via TBK1-OPTN phosphorylation, revealing a critical mechanistic intersection with the RED and BLUE streams of the disease model: in SAMHD1 haploinsufficiency, chronic cGAS-STING activation would simultaneously drive IFN-I (canonical) and dysregulate mitophagy quality control (non-canonical), and disruption of the STING1-TBK1-OPTN axis shifts cell fate toward apoptosis rather than pro-survival mitophagy, directly explaining the double mitophagy block and accumulation of damaged mitochondria central to the family's interferon-mitochondrial syndrome.
DOI: 10.1080/15548627.2026.2689463

cGAS-STING signaling pathway: a central pathological mechanism and emerging therapeutic target for postoperative cognitive dysfunction. (from Anesthesiology/Perioperative Neuroscience)
Wu Xiaoqin; Zhong Baolin; Xu Yongxing; Lai Yinsiqing; Wen Xinming — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target

This review directly describes the mtDNA-cGAS-STING-neuroinflammation axis with pyroptosis and mitophagy failure as central mechanisms, which maps precisely onto the BLUE and RED streams of the SAMHD1 haploinsufficiency model, and identifies cGAS-STING inhibition and mitophagy promotion as therapeutic targets directly applicable to this disease mechanism.
DOI: 10.1016/j.brainres.2026.150432

Runx1-Snx9 axis drives the pathological secretion of mitochondrial-derived vesicles to activate cGAS-STING signaling in acute pancreatitis. (from Gastroenterology/Pancreatology)
Gao Mengqi; Xiao Guohui; Chen Kunhao; Li Shiyu; Chen Cong — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, NLRP3, other

This paper directly characterizes a novel upstream mechanism (Runx1-Snx9 axis) driving mitochondrial-derived vesicle secretion and mtDNA release that activates macrophage cGAS-STING signaling — the same BLUE stream pathway central to SAMHD1 haploinsufficiency — providing a mechanistic parallel for how cytosolic/extracellular mtDNA fragments trigger chronic interferon activation, even though the context is acute pancreatitis rather than SAMHD1 dysfunction.
DOI: 10.1186/s12951-026-04687-6

Environmental enrichment mitigates sevoflurane-induced neurodevelopmental injury via cGAS-STING-dependent microglial modulation. (from Pediatric anesthesiology/neurodevelopment)
Li Feixiang; Gong Bingqing; Wu Haiyan; Yang Yongyan; Luo Ying — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, ME-CFS, other

This paper directly demonstrates the mitochondrial dysfunction → mtDNA release → cGAS-STING activation → microglial neuroinflammation → synaptic/cognitive impairment axis, which is mechanistically identical to the BLUE stream in the SAMHD1 haploinsufficiency model, and validates mtDNA-driven cGAS-STING as a tractable intervention target in a neurodevelopmental context relevant to the AuDHD phenotype in the proband.
DOI: 10.1186/s13578-026-01610-2

Beyond proteostasis: LONP1 as an immunometabolic checkpoint in health and disease. (from Mitochondrial biology / proteostasis)
Xie Lin; Wu Li-Hong; Ni Xin-Cheng; Zhang Jiang-Nan — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, NLRP3, VDAC1, mTOR-lysosomal, ME-CFS, treatment-target, other

LONP1 directly regulates mtDNA maintenance and its deficiency triggers mtDNA release activating cGAS-STING—the BLUE stream core mechanism in this disease—while also modulating metabolic enzymes relevant to the mitochondrial-inflammatory convergence and SARS-CoV-2 pathogenesis relevant to ME/CFS post-viral trigger, making this a high-value adjacent mechanism with novel treatment implications.
DOI: 10.1016/j.bcp.2026.118170

Mitophagy in Macrophages: A Metabolic Checkpoint in Inflammation-to-Repair Transition in Atherosclerosis. (from Cardiology/atherosclerosis)
Jie Zhou; Hanxiu Liu; Sen Ma; Haoyang Wang; Ni He — Journal of the American Heart Association 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, treatment-target, POLG-mtDNA

This review directly covers the RED and BLUE stream mechanisms—PINK1/Parkin mitophagy block, mtDNA release activating cGAS-STING and NLRP3 inflammasome in macrophages—with therapeutic targets (metformin, resveratrol, MCC950-analogous NLRP3 inhibition) that map precisely onto the ISG15-mitophagy double-block and VDAC1-cGAS-STING axes central to the SAMHD1 haploinsufficiency syndrome, though SAMHD1 itself is not mentioned.
DOI: 10.1161/jaha.125.048103

The COX2-PGE2-PKA Axis Suppresses Antiviral Immunity by Inhibiting mtDNA-Dependent STING Activation (from Virology/innate immunity (HSV-1 infection model))
P. Vo; Julien Cicero; Zichen Wang; Hiroyuki Hakozaki; Thomas S. Hoang — bioRxiv 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, ISG15-mitophagy, ME-CFS, treatment-target

This paper directly addresses the mtDNA-cytosol-cGAS-STING-IFN-I axis (BLUE stream) and mitophagy regulation thereof, revealing that COX2/PGE2/PKA/STOML2 suppresses STING activation by clearing immunostimulatory cytosolic mtDNA via mitophagy—a regulatory circuit highly relevant because in SAMHD1 haploinsufficiency the mtDNA-cGAS-STING pathway is constitutively overactivated and the ISG15/MFN1/MFN2 mitophagy block prevents this clearance, making COX2/PGE2/PKA axis modulation a potential therapeutic lever.
DOI: 10.64898/2026.04.03.716411

Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis (from Cardiology/Vascular biology)
Hao Liu; Shuai Zhao; Huiqin Gao; Yue Wang; Junyan Gao — Precision Clinical Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, JAK-STAT, POLG-mtDNA, treatment-target

This review directly covers the core convergent mechanism of the disease profile—mt-DAMPs (including mtDNA escape via mitochondrial membrane permeability changes analogous to VDAC1 macropore opening) activating cGAS-STING to drive type I interferon production and NLRP3-mediated IL-1β release—while also detailing the PINK1-Parkin mitophagy pathway that is blocked by ISGylation of MFN1/MFN2 in the RED stream, providing mechanistic depth and atherosclerosis-relevant treatment targets applicable to the interferonopathy-mitochondrial syndrome.
DOI: 10.1093/pcmedi/pbag010

Cytosolic Immunostimulatory DNA Ligands and DNA Damage Activate the Integrated Stress Response, Stress Granule Formation, and Cytokine Production (from Cancer immunotherapy / DNA damage biology)
Trupti Devale; Lekhana Katuri; Gauri Mishra; Aditya Acharya; Praveen Manivannan — Cells 2026
Score: 7/10 | Pathways: cGAS-STING, JAK-STAT, ME-CFS, treatment-target, other

This paper directly characterizes the STING-PERK-G3BP1 signaling axis linking cytosolic dsDNA sensing (including mtDNA escape, the core BLUE pathway) to the integrated stress response, stress granule formation, and IFN-I/cytokine production — mechanisms directly downstream of SAMHD1 haploinsufficiency-driven dNTP pool expansion and VDAC1-mediated mtDNA release, and identifies PERK as a novel druggable node that could modulate the chronic interferonopathy in this family.
DOI: 10.3390/cells15020139

🟡 Medium Relevance (Score 5–6)

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Restoring BECN1-Mediated Autophagy Mitigates Acute Lung Injury Caused by Zinc Oxide Nanoparticles. (from Pulmonary toxicology/nanotoxicology)
Lejiao Mao; Meiling Tan; Xuejun Jiang; Jun Zhang; Ge Xu — Free radical biology & medicine 2026
Score: 6/10 | Pathways: ISG15-mitophagy, NLRP3, mTOR-lysosomal, treatment-target

This paper directly demonstrates that BECN1 haploinsufficiency (heterozygous knockout) impairs mitophagy flux causing accumulation of dysfunctional mitochondria, ROS, and inflammatory cascades—mechanistically parallel to the RED stream where ISGylation of BECN1 blocks autophagy flux in the SAMHD1 disease model, and validates Tat-Beclin1 as a pharmacological rescue strategy for BECN1-dependent mitophagy failure.
DOI: 10.1016/j.freeradbiomed.2026.05.317

Immunoglobulin G complexes from post-infectious ME/CFS, including post-COVID ME/CFS disrupt cellular energetics and alter inflammatory marker secretion (from Neuroimmunology/autoimmunity)
Zheng Liu; Claudia Hollmann; S. Kalanidhi; S. Lamer; Andreas Schlosser — Brain, Behavior, & Immunity - Health 2026
Score: 6/10 | Pathways: ME-CFS, VDAC1, ISG15-mitophagy, JAK-STAT, clinical-phenotype, other

This paper directly characterizes ME/CFS (including post-COVID ME/CFS) IgG-mediated mitochondrial fragmentation and energetic disruption in endothelial cells, providing mechanistic autoimmune context for the proband's post-viral ME/CFS phenotype, with mitochondrial fragmentation highly relevant to the ISG15-MFN1/2 mitophagy block and VDAC1 macropore streams in the disease model.
DOI: 10.1016/j.bbih.2026.101187

Interferon stimulatory DNA activates the DNA damage signaling through ATM and DNA-PK sensing (from DNA damage response / genome stability)
Samira Kemiha; Lorena Rejón-Franco; Estelle Ghibaudo; R. Eloiflin; Morgane Chema — The Journal of Biological Chemistry 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, ME-CFS, other

This paper demonstrates that cytoplasmic ISD (the same stimulus generated by VDAC1-mediated mtDNA escape in the BLUE stream) co-activates ATM and DNA-PK damage response kinases independently of cGAS-STING, revealing a parallel DDR arm that could amplify genomic instability and checkpoint activation in SAMHD1 haploinsufficiency where chronic cytosolic dsDNA (from ox-mtDNA fragments) is present.
DOI: 10.1016/j.jbc.2026.111362

African swine fever virus pE199L, as a mitophagy receptor, suppresses antiviral innate immunity to promote viral replication. (from Veterinary virology / ASFV vaccinology)
Xiaoxuan Li; Binbin Ren; Danyang Zhang; Miao Dan; Dongying Liu — Autophagy 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, ME-CFS, other

This paper directly addresses the cGAS-STING pathway and PINK1/Parkin-dependent mitophagy as targets of viral immune evasion—mechanisms central to the SAMHD1 A565T syndrome—demonstrating that mitophagic clearance of TBK1 suppresses type I interferon production, which is the inverse of the constitutive IFN-I overactivation and mitophagy block seen in this family, providing mechanistic insight into how mitophagy flux regulation gates cGAS-STING-IFN-I signaling amplitude.
DOI: 10.1080/15548627.2026.2654982

B33-01 Cisd1 Regulates the Sting Pathway Through the Ubiquitin-proteasome System to Ameliorate COPD Progression (from Pulmonology/COPD)
J. Gao; Y. Song — American Journal of Respiratory and Critical Care Medicine 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, other

This paper describes a mitochondria-to-STING innate immunity axis where CISD1 (a mitochondrial iron-sulfur protein) regulates STING degradation via K48-ubiquitination through Ubr5, directly engaging the cGAS-STING-TBK1-IRF3 pathway that is a core loop (BLUE) in the SAMHD1 haploinsufficiency mechanism, offering a novel STING regulatory checkpoint (ubiquitin-proteasome degradation) relevant to modulating the chronic interferon signature seen in the family, though SAMHD1 and dNTP biology are not addressed.
DOI: 10.1093/ajrccm/aamag162.1786

Toward a Molecular Reclassification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Integrating Multi-Omics, Machine Learning, and Precision Medicine (from Computational biology / precision medicine / multi-omics)
Joshua Frank; Nicole Nesterovitch; Chetana Movva; N. Klimas; L. Nathanson — International Journal of Molecular Sciences 2026
Score: 6/10 | Pathways: ME-CFS, JAK-STAT, POLG-mtDNA, cGAS-STING, NLRP3, ISG15-mitophagy, treatment-target, other

This review directly addresses ME/CFS molecular reclassification and identifies chronic innate immune activation, mitochondrial dysfunction, and genetic risk variants as core pathophysiology—all of which map onto the SAMHD1 A565T interferon-mitochondrial syndrome mechanism—but does not specifically implicate SAMHD1, cGAS-STING, or the dNTPase axis, making it a high-quality contextual reference for the proband's ME/CFS phenotype rather than a mechanistic confirmation.
DOI: 10.3390/ijms27104436

Ca2+-driven self-amplified nanoplatform targeting ER-mitochondrial calcium crosstalk for synergistic apoptosis induction and tumor immune microenvironment remodeling (from Oncology/nanomedicine)
Yucui Ding; Xinyu Liu; Jianlong Fu; Jianyue Xue; Xueni Fan — Materials Today Bio 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, NLRP3, other

The paper directly engages the IP3R-GRP75-VDAC complex, mitochondrial permeability transition, and Mn2+-driven cGAS-STING activation—all mechanistically overlapping with the BLUE and PURPLE streams of the SAMHD1 interferonopathy model—but in an oncology/nanomedicine context with no connection to SAMHD1 haploinsufficiency, dNTP pool dysregulation, or the family's clinical phenotypes.
DOI: 10.1016/j.mtbio.2026.103339

Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics (from Virology/Retrovirology)
K. D. Perera; E. Oltra; S. Carding — International Journal of Molecular Sciences 2026
Score: 5/10 | Pathways: ME-CFS, cGAS-STING, JAK-STAT, AGS-spectrum, other

The paper addresses ME/CFS pathogenesis through HERV-driven innate immune activation (including cGAS-STING sensing, LTR-driven interferon amplification, and JAK-STAT signaling) which overlaps mechanistically with the IFN-I loop central to SAMHD1 haploinsufficiency syndrome, and HERV reactivation is plausibly potentiated by the dNTP pool expansion that SAMHD1 normally suppresses (since SAMHD1 restricts retrotransposon/HERV reverse transcription), but the paper does not address SAMHD1, VDAC1, NLRP3, mitochondrial pathways, or ISG15-mitophagy directly.
DOI: 10.3390/ijms27104309

Dual-targeting macrophage membrane nanosystem enhances radiotherapy-induced antitumor immunity via synergistic nuclear and mitochondrial DNA damage. (from Oncology/Nanomedicine)
Guangyu Ju; Qi Ding; Hongcang Gu; Rao Liu; Xiao Liu — Biomaterials science 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, JAK-STAT, other

This paper demonstrates that mitochondrial membrane permeabilization (analogous to VDAC1 macropore opening in the BLUE stream) causes cytosolic accumulation of mitochondrial nucleic acids activating innate immune signaling and type I interferon, which mechanistically parallels the SAMHD1/VDAC1-mtDNA-cGAS-STING axis, but the context is engineered radiotherapy enhancement in glioma with no SAMHD1 involvement.
DOI: 10.1039/d6bm00279j

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

TFEB-mediated autophagy dysregulation links with PRPF31 deficiency-induced photoreceptor death via PLK4 downregulation. (from Ophthalmology/retinal genetics)
Lujia Zhang; Yuntao Qu; S. Yao; Luying Han; Guangming Liu — Experimental eye research 2026
Score: 4/10 | Pathways: mTOR-lysosomal, other

This paper describes a haploinsufficiency-driven autophagic hyperactivation and mitochondrial dysfunction cascade (PLK4-TFEB axis) that shares conceptual overlap with the lysosomal/autophagy failure and mitochondrial damage themes in the SAMHD1 syndrome, but involves entirely different genes (PRPF31, PLK4, TFEB) in a retinal degeneration context with no connection to interferon signaling, dNTP metabolism, cGAS-STING, or any other core SAMHD1 pathway.
DOI: 10.1016/j.exer.2026.111000

C-terminal tail of MAVS dictates organelle targeting and innate immune response (from Cell biology / virology)
Terence Lee; Kiki Cham; Dong-Yan Jin — Cell Communication and Signaling : CCS 2026
Score: 4/10 | Pathways: cGAS-STING, other

MAVS organelle-specific signaling is upstream of IRF3/IFN-β activation (a convergent endpoint in the BLUE stream), but this paper addresses RNA sensing via RIG-I-like receptors rather than the cGAS-STING/VDAC1-mtDNA axis central to SAMHD1 haploinsufficiency, making the connection tangential despite sharing IRF3 and type I interferon as readouts.
DOI: 10.1186/s12964-026-02753-y

Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation. (from Virology/RNA biology)
Djamal Brahim Belhaouari; Anil Pant; Santiago Navarro-Forero; Fernando Cantu; Zh — Proceedings of the National Academy of Sciences of the United States of America 2026
Score: 4/10 | Pathways: POLG-mtDNA, ME-CFS, other

This paper reveals an interferon-independent mechanism by which RNA accumulation directly impairs mitochondrial membrane potential and respiration, which is tangentially relevant as the SAMHD1 haploinsufficiency model involves mitochondrial dysfunction, but the paper's core mechanism (excess RNA perturbing mitochondria during poxvirus infection) is not a primary pathway in the SAMHD1 A565T disease model and involves no direct overlap with cGAS-STING, VDAC1, ISG15, NLRP3, or dNTPase axes.
DOI: 10.1073/pnas.2605194123

Genetic and transcriptomic signatures of host control in HIV-1 infection. (from Infectious disease / virology)
Oreshkov Sergey; Thorball Christian W; Meylan Jenny; Muriset Maude; Calmy Alexan — 2026
Score: 3/10 | Pathways: dNTPase, other

This paper identifies SAMHD1 as an HIV-1 restriction factor counteracted by Vpx in passing, but focuses on transcriptomic correlates of HIV load control rather than SAMHD1 dNTPase function, haploinsufficiency, or the cGAS-STING/interferonopathy/mitochondrial pathways central to the disease profile.
DOI: 10.1186/s12977-026-00679-4

Degradable STING nanomodulators orchestrate the innate-to-adaptive immune response for NIR-II photothermal-immunotherapy via a cancer-immunity cycle (from Nanomedicine/oncology)
Qiaolin Wei; Zirui Zhu; Yue Li; Siying Sun; Ge Gao — Materials Today Bio 2026
Score: 3/10 | Pathways: cGAS-STING, other

While this paper involves cGAS-STING pathway activation, it does so in the context of engineered cancer nanoparticle immunotherapy using exogenous Zn2+/ROS/photothermal stimulation in solid tumors, with no mechanistic relevance to SAMHD1 haploinsufficiency, endogenous dNTP pool dysregulation, interferonopathy, or any of the family's clinical phenotypes.
DOI: 10.1016/j.mtbio.2026.103028

Bispecific Macrophage Nano-Engager Couples Dual Checkpoint Blockade with Stimulator of Interferon Genes Activation to Potentiate Antitumor Immunity. (from Oncology/Nanomedicine)
Bao-Toan Dang; Khang-Yen Pham; Huyen T. Le; Thoa Thi Kim Nguyen; A. T. Vu — ACS nano 2026
Score: 3/10 | Pathways: cGAS-STING, JAK-STAT, other

This paper activates STING pharmacologically (SR717 agonist) in a tumor immunotherapy context, which is mechanistically opposite to the disease profile where cGAS-STING is pathologically overactivated by cytosolic mtDNA fragments; the paper's engagement with STING/IFN pathways is incidental to its oncology focus and offers no direct mechanistic insight into SAMHD1 haploinsufficiency or the interferonopathy cascade.
DOI: 10.1021/acsnano.6c01144

Pathway Coverage This Week

  • cGAS-STING: 21 papers
  • other: 20 papers
  • POLG-mtDNA: 15 papers
  • VDAC1: 12 papers
  • treatment-target: 12 papers
  • ME-CFS: 11 papers
  • ISG15-mitophagy: 10 papers
  • NLRP3: 9 papers
  • JAK-STAT: 8 papers
  • mTOR-lysosomal: 4 papers
  • dNTPase: 2 papers
  • clinical-phenotype: 2 papers
  • urate-NLRP3: 1 papers
  • AGS-spectrum: 1 papers

SAMHD1 Research Digest — 2026-06-14

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 41 papers evaluated | 12 high-relevance (≥7) | 17 medium (5–6) | 12 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Spotlight on cGAS-STING: role in disease pathogenesis and therapeutic potential. (from Ophthalmology (senior author Liu Zuguo is an ophthalmologist, suggesting ocular surface/corneal innate immunity application))
Yan Dan; Hu Jiaoyue; Liu Zuguo; Ouyang Weijie — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, JAK-STAT, NLRP3, POLG-mtDNA, treatment-target, AGS-spectrum, ME-CFS

This comprehensive review directly covers the BLUE stream (cGAS→cGAMP→STING→IRF3→IFN-I) that is central to the SAMHD1 A565T mechanism, including mitochondrial/micronuclear DNA sensing, liquid-liquid phase separation dynamics, metabolic-immune crosstalk, neurodegenerative and autoimmune contexts, and emerging small-molecule inhibitors (including cGAS inhibitors like IMSB301-class compounds) that represent direct therapeutic targets for this interferonopathy.
DOI: 10.1186/s43556-026-00478-5

Mitochondria as convergence hubs for innate immunity pathways. (from Cell biology / mitochondrial biology)
Guo Yunhao; Xue Yansong — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, ME-CFS, other

This review directly addresses the convergence of mitochondria as innate immune signaling hubs integrating cGAS-STING, NLRP3, and MAVS pathways through mitochondrial DAMPs—precisely the mechanistic framework (BLUE, PURPLE, RED streams) underlying the SAMHD1 A565T interferonopathy, linking mitochondrial dysfunction to autoimmunity and offering therapeutic pathway insights.
DOI: 10.1038/s42003-026-10479-3

Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis. (from Neurology/Neuroimmunology)
Liu Yongqing; Ye Yingzhi; Fan Minghua; Cheng Henry Yi; Sun Shuying — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, dNTPase, treatment-target, other

This paper directly demonstrates the mechanistic axis of cytosolic mtDNA release → cGAS-STING → NLRP3 chronic neuroinflammation in microglia, and critically implicates Cmpk2 (a mitochondrial dNTP kinase regulating mtDNA synthesis) as a regulatory node—directly paralleling SAMHD1's role in dNTP pool control and mtDNA-driven innate immune activation in the BLUE and PURPLE pathways, with KAT7 inhibition as a pharmacologically tractable intervention point.
DOI: 10.1016/j.neuron.2026.05.015

A pore is a pore is a pore (or a hub?): VDAC oligomerization in mitochondrial connectivity and modulation. (from Structural biology / mitochondrial biophysics)
De Pinto Vito; Battiato Giuseppe; Conti-Nibali Stefano; Cubisino Salvatore Anton — 2026
Score: 8/10 | Pathways: VDAC1, cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, ISG15-mitophagy

This review directly covers VDAC1 oligomerization, macropore formation, mtDNA escape mechanisms, outer mitochondrial membrane permeabilization, and emerging small-molecule modulators (including VBIT-4 class compounds), all of which are central to the BLUE stream (SAMHD1/VDAC1 interaction loss → VDAC1 macropore → cytosolic mtDNA → cGAS-STING-IRF3-IFN-I) in the disease mechanism, and discusses therapeutic targeting strategies directly applicable to this interferonopathy.
DOI: 10.1042/bst20250480

Mitochondrial kinase CMPK2 in immune homeostasis and disease: from metabolic regulation to inflammatory signaling. (from Biochemistry/Virology)
Junhu Yao; Mengjie Shi; Siyan Chen; Huan Zhang; Yiming Lin — International immunopharmacology 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, dNTPase, ME-CFS, treatment-target, other

CMPK2 is a mitochondrial nucleotide kinase that directly links mitochondrial dNTP pool regulation (UTP/CTP synthesis for mtDNA replication) to both NLRP3 inflammasome activation and cGAS-STING signaling via oxidized/escaped mtDNA, positioning it as a mechanistic neighbor to SAMHD1's dNTPase deficiency cascade, with additional relevance to SARS-CoV-2/post-viral contexts and SLE interferonopathy overlapping the AGS spectrum.
DOI: 10.1016/j.intimp.2026.116582

MitoSafe hypothesis: safeguarding mitochondrial morphology and innate immunity. (from Cell biology / mitochondrial biology)
Nora Haggerty; Kentaro Nakamura; H. Sesaki; M. Iijima — Trends in cell biology 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, POLG-mtDNA, ME-CFS

This paper directly addresses PINK1/Parkin-mediated mitophagy dysregulation leading to mitochondrial enlargement, mtDNA release, and STING-mediated inflammation — precisely the RED and BLUE pathway loops in the SAMHD1 haploinsufficiency mechanism where ISGylation of MFN1/MFN2 blocks PINK1/Parkin mitophagy, causing damaged mitochondrial accumulation, mtDNA escape, and cGAS-STING activation.
DOI: 10.1016/j.tcb.2026.04.007

Neuroprotection by lactate in Parkinson's disease: A novel anti-inflammatory mechanism via 14-3-3 protein lactylation. (from Neurology/Neurodegeneration (Parkinson's disease))
Zhang Qi; Liu Ming; Cao Wen-Jing; Zou Wei; Zhang Ping — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the mechanistic triad central to SAMHD1 haploinsufficiency pathology—NLRP3 inflammasome activation, cytosolic mtDNA release, and cGAS-STING pathway engagement—and shows that lactate/14-3-3 lactylation can interrupt this loop at multiple nodes (NLRP3 suppression → reduced GSDMD-driven mitochondrial injury → decreased cytosolic mtDNA → attenuated cGAS-STING), identifying lactate signaling as a novel upstream brake on the BLUE and PURPLE pathway convergence points relevant to the disease mechanism.
DOI: 10.1016/j.bbadis.2026.168314

A Narrative Review of the mtDNA-Stimulated Inflammatory Axis in Sepsis-Induced Acute Lung Injury: Cellular Mechanisms and Therapeutic Targeting. (from Critical care / pulmonology)
Ma Shuqi; Pan Qiusha; Zeng Ruifeng; Liu Quanle; Yang Suyi — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target, other

This review directly covers the mtDNA-cGAS-STING-NLRP3 inflammatory axis with cell-type-specific mechanistic detail and therapeutic targeting strategies (STING inhibitors, MCC950-class NLRP3 blockers) that map precisely onto the BLUE and PURPLE pathways of SAMHD1 haploinsufficiency, where cytosolic mtDNA escape via VDAC1 macropores drives chronic interferonopathy and pyroptosis, making it highly mechanistically relevant even though SAMHD1 is not mentioned.
DOI: 10.1093/jleuko/qiag077

Small but mighty: mitochondrial DNA at the centre of retrograde signalling (from Cell biology / mitochondrial biology)
Eve Harding; Veronica Bazzani; C. Vascotto — Cell Communication and Signaling : CCS 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, dNTPase, ME-CFS, other

This review directly addresses mtDNA escape, retrograde signalling via cGAS-STING innate immune activation, POLG/mtDNA instability, and mitochondrial dynamics—all core mechanistic streams of the SAMHD1 A565T syndrome—making it highly relevant as a mechanistic framework paper despite lacking direct SAMHD1 data.
DOI: 10.1186/s12964-026-02858-4

Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies (from hepatology/transplant surgery)
Ruotong Shen; Peng An; Meng Chen; Ping Lu; Jingjing Yang — Journal of Translational Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target, other

This paper directly elaborates the mtDNA-release → cGAS-STING → NLRP3 inflammasome → pyroptosis vicious cycle that constitutes the BLUE and PURPLE mechanistic streams of the SAMHD1 haploinsufficiency syndrome, covering VDAC1 permeability, mitophagy failure, and pharmacological intervention points (cGAS-STING and NLRP3 inhibition) directly relevant to therapeutic targeting in the family's interferonopathy.
DOI: 10.1186/s12967-026-08155-5

From symbiosis to immunity: the evolutionary revival of mitochondrial defense programs in inflammatory diseases (from Evolutionary biology / mitochondrial biology)
Weilong Hong; Shiyu Long; M. Ashrafizadeh; Gautam Sethi; Chenyang Duan — Cell Communication and Signaling : CCS 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, ME-CFS, other

This review directly addresses the core convergence of mitochondrial dysfunction, mtDNA release, DAMP-driven innate immune activation (cGAS-STING, NLRP3), and mitophagy failure that constitutes the mechanistic heart of the SAMHD1 A565T interferonopathy model, including VDAC1-mediated mtDNA escape and the progression from mitochondrial stress to systemic inflammatory amplification, though SAMHD1 itself is not mentioned.
DOI: 10.1186/s12964-026-02736-z

Understanding cardiovascular aging as a disorder of mitochondrial network (from Cardiology)
Taslima Akter Shila; Dhrubo Ahmad; Jianli Zhao; Huilan Tan; Bo Wang — The Journal of Cardiovascular Aging 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, POLG-mtDNA, NLRP3, treatment-target, clinical-phenotype

This review directly covers mtDNA release activating cGAS-STING, mitophagy/fission-fusion defects, and mitochondrial network dysfunction driving sterile inflammation — all core RED/BLUE/PURPLE stream mechanisms in the SAMHD1 haploinsufficiency model — with cardiovascular aging implications relevant to the family's interferonopathy-cardiac phenotype risk.
DOI: 10.20517/jca.2026.07

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles. (from Geroscience/aging biology)
Xiang Zijie; Chen Yu; Liu Xishui; Lu Haowen; Yang Yuqing — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, mTOR-lysosomal, treatment-target, other

This review systematically covers mitochondrial dysfunction mechanisms directly relevant to the disease model—including cGAS-STING activation by escaped mtDNA, mitophagy failure, mitochondrial dynamics (MFN1/MFN2-related), biogenesis (PGC-1alpha), and mtDNA instability—and surveys therapeutic strategies (including mitochondrial transplantation and base editing) that could apply to SAMHD1 haploinsufficiency's convergent interferon-mitochondrial syndrome, though it does not address SAMHD1 specifically.
DOI: 10.1002/mco2.70790

Intrinsically Mitochondria-Targeting Nanozyme via Coordination-Assembly of Natural Quercetin for Cascade Antioxidant Therapy of Cerebral Ischemia-Reperfusion Injury. (from Nanomedicine/Neurology)
Zheng Wenxuan; Wang Zhicheng; Zhou Xin; Wang Shuya; Shi Xiaojing — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the mtDNA leakage → cGAS-STING neuroinflammatory axis (core BLUE stream) and shows that stabilizing mitochondrial outer membrane proteins (including VDAC1-related outer membrane targets) prevents mtDNA escape, offering mechanistic and therapeutic parallels to the SAMHD1 haploinsufficiency syndrome's central pathogenic loop, though it is framed in cerebral ischemia-reperfusion rather than interferonopathy or SAMHD1 contexts.
DOI: 10.1002/advs.76038

Size-dependent ruthenium/ceria nanozymes synchronize catalytic ROS scavenging and electrostatic mtDNA sequestration for periodontitis therapy. (from Dental/biomaterials nanomedicine)
Zhang Fanrou; Qi Manlin; Liu Jia; Du Juanrui; Shi Fangyu — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, NLRP3, treatment-target, other

This paper directly addresses the mtDNA escape → cytosolic mtDNA → innate immune activation axis (core BLUE pathway) and mitochondrial oxidative stress, proposing electrostatic sequestration of cytosolic mtDNA as a therapeutic strategy that could conceptually apply to SAMHD1-driven cGAS-STING activation, though it is disease-specific to periodontitis and not mechanistically linked to SAMHD1 or dNTPase dysfunction.
DOI: 10.1186/s12951-026-04660-3

Sex Differences in Mitochondrial Function: Endocrine Regulation, Immunometabolic Signaling, and Implications for Health and Disease. (from Endocrinology/reproductive biology)
Bynum Hanna; Edwards Kristin S — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, JAK-STAT, ME-CFS, treatment-target, pregnancy-fetal, other

This review directly covers mtDNA release activating cGAS-STING, NLRP3 inflammasome, and mitochondrial quality control pathways central to the SAMHD1 A565T mechanism, and addresses sex-hormone modulation of mitochondrial biogenesis, ROS, and immunometabolic signaling that would modulate disease expression across the multi-generational family, but does not address SAMHD1 specifically or dNTP pool dynamics.
DOI: 10.3390/ijms27114966

No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases (from Mitochondrial disease / clinical genetics)
M. Marchais; Alessandra Pennisi; Alexandre Pierga; A. Lepelley; Nicolas Cagnard — European Journal of Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, JAK-STAT, ME-CFS, other

This paper directly interrogates the cGAS-STING axis and cytosolic mtDNA leakage in patient fibroblasts with mitochondrial disease, finding that ISG elevation and mtDNA escape are dissociated—a critical negative finding that complicates the BLUE/PURPLE pathway model where VDAC1-mediated mtDNA escape drives IFN-I in SAMHD1 haploinsufficiency, and raises important methodological cautions about using fibroblast models to validate the proposed SAMHD1 A565T interferon-mitochondrial mechanism.
DOI: 10.1002/eji.70176

Advances in Elucidating the Mitochondrial DNA Mechanisms Underlying Ozone-Induced Inflammation (from Environmental toxicology/pulmonology)
Qian Chen; Hao Liu; Junhe Zhou; Yongjie Wei; Lingyan He — Toxics 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ME-CFS, other

This review directly addresses mtDNA escape from dysfunctional mitochondria as a DAMP activating innate immune/inflammatory pathways (cGAS-STING, NLRP3), which mirrors the BLUE and PURPLE mechanistic streams of SAMHD1 haploinsufficiency, though the upstream trigger is ozone rather than dNTP pool expansion via SAMHD1 loss.
DOI: 10.3390/toxics14030248

Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects (from Cardiology)
Mingyang Ni; Aijia Zheng; Hang Zheng; Wenqing Jia; Yuansheng Wang — Frontiers in Cardiovascular Medicine 2026
Score: 6/10 | Pathways: POLG-mtDNA, cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, clinical-phenotype, other

This review directly addresses mtDNA mutation-driven innate immune activation (cGAS-STING, NLRP3), mitochondrial structural dysfunction (VDAC1, dynamics), oxidative stress, and metabolic reprogramming in cardiac disease — all core loops of the SAMHD1 interferonopathy mechanism — with cardiology phenotype relevance given the family's interferonopathy-driven mitochondrial cardiomyopathy risk, though SAMHD1 itself is not mentioned.
DOI: 10.3389/fcvm.2026.1781927

Lethal effects of a hyperactive dGTP triphosphohydrolase in E. coli. (from microbiology/biochemistry)
Bhawsinghka Niketa; Glenn Katie F; Klemm Bradley P; Singh Deepa; Day Ryan C — 2026
Score: 5/10 | Pathways: dNTPase, POLG-mtDNA, other

This paper directly investigates the consequences of hyperactive dGTPase activity causing dGTP depletion and chromosomal disruption in E. coli, which is mechanistically inverse but conceptually adjacent to the SAMHD1 haploinsufficiency disease model where reduced dNTPase activity causes dGTP pool expansion — both scenarios underscore the critical importance of precise dNTP pool regulation, particularly dGTP, for genomic integrity and cell viability.
DOI: 10.1093/genetics/iyag139

Mitochondrial Metabolic Reprogramming in Colorectal Cancer-Associated Fibroblasts: An Up-to-Date Review. (from Oncology/Cancer Biology)
Li Ying; Chanda Dipanjan; Jeon Seong-Woo; Jeon Jae-Han; Kim Min-Ji — 2026
Score: 5/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, mTOR-lysosomal, other

This review covers CAF mitochondrial reprogramming in CRC and explicitly discusses mtDNA-mediated cGAS-STING signaling, AMPK-PGC-1α, mitophagy/fission-fusion dynamics, and ROS-NF-κB pathways that are directly mechanistically relevant to the SAMHD1 interferonopathy model, but the context is tumor-stroma crosstalk rather than germline interferonopathy or dNTPase haploinsufficiency, making the connection indirect.
DOI: 10.3390/cancers18111786

Manganese Vacancy-Engineered Prussian Blue Triggers Pyroptosis-Driven Innate Immunity for Second Near-Infrared Region Photoimmunotherapy. (from Oncology/Nanomedicine)
Wang Xiaorui; Li Runtao; Wang Ye; Li Yunpeng; Liu Liren — 2026
Score: 5/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, other

This paper demonstrates the mechanistic link between ROS-induced gasdermin E-mediated pyroptosis, cytosolic mtDNA release, and cGAS-STING activation—pathways directly relevant to the SAMHD1 disease model—but in an engineered oncology/photoimmunotherapy context that is mechanistically informative but clinically distant from haploinsufficiency-driven interferonopathy.
DOI: 10.1021/acsnano.6c05567

Barrier-to-autointegration factor protects against the cGAS-STING response to chromatin bridges. (from Cell biology / mitosis)
Chastant Laura; Normandin Karine; El-Mortada Firas; Servant Marc J; Archambault * — 2026
Score: 5/10* | Pathways: cGAS-STING, other

This paper characterizes BAF (Barrier-to-Autointegration Factor) as a suppressor of cGAS-STING activation via chromatin bridge stabilization—a nuclear/mitotic mechanism distinct from the SAMHD1/VDAC1/mtDNA route, but confirming that cGAS-STING can be potently activated by aberrant chromatin structures and that IRF3-dependent proinflammatory transcription results; relevant as contextual mechanistic background for the BLUE stream but does not touch SAMHD1, mitochondria, dNTP pools, or any family phenotype directly.
DOI: 10.1371/journal.pgen.1012191

Acacetin ameliorates MASLD by inhibiting the Notch1 pathway in hepatocytes and reprogramming macrophage polarization via Keap1-Nrf2-mediated restraint of ferroptosis. (from Hepatology)
Xu Jun; Ying Huiya; Wang Yixiao; Zeng Yuan; Zhao Qian — 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, IRF7-metabolic, NLRP3, treatment-target, other

The paper directly demonstrates that mitochondrial injury drives mtDNA release activating cGAS-STING in macrophages (a core BLUE-stream pathway in the disease model), and documents hepatic steatosis/MASLD — a tracked family phenotype — but the mechanism is studied in a non-SAMHD1 context with no connection to dNTPase haploinsufficiency, making it an adjacent mechanistic parallel rather than a direct hit.
DOI: 10.1016/j.metabol.2026.156670

Mitochondrial OXPHOS restricts SARS-CoV-2 replication. (from virology/cell metabolism)
Soto Albrecht Yentli E; Morrow Ryan M; Kenney Devin; Olali Arnold Z; Wacquiez Al — 2026
Score: 5/10 | Pathways: POLG-mtDNA, ME-CFS, dNTPase, other

This paper demonstrates that mitochondrial OXPHOS suppresses SARS-CoV-2 replication via metabolic balance rather than innate immune differences, which is indirectly relevant because the SAMHD1 A565T haploinsufficiency causes mitochondrial dysfunction (via POLG stalling, perturbed dNTP pools, and OXPHOS impairment), potentially creating a permissive environment for enhanced SARS-CoV-2 replication and post-viral ME/CFS triggering in the proband, but the paper explicitly rules out innate immune pathway differences as the mechanism, limiting its direct relevance to the cGAS-STING/interferonopathy axis central to this disease.
DOI: 10.1126/sciadv.adz3081

Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion (from Oncology)
Fan Yang; Rui Liu; Li Liu; Aijie Zhang; Bo Li — Frontiers in Immunology 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, other

This review covers cGAS-STING, type I interferon, and innate immune evasion mechanisms directly relevant to the SAMHD1 interferonopathy framework, including metabolic reprogramming and ubiquitin-mediated regulation, but the lung cancer focus and lack of SAMHD1, NLRP3, VDAC1, or mitophagy content limits direct applicability to the disease profile.
DOI: 10.3389/fimmu.2026.1842558

The human cytomegalovirus vMIA protein inhibits apoptosis and innate immune signaling in human Mueller cells. (from ophthalmology/virology)
M. M. Sauter; H. Noel; Curtis R. Brandt — Experimental eye research 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, ME-CFS, other

The paper demonstrates viral modulation of the cGAS-STING pathway and mitochondrial apoptosis signaling via vMIA, which intersects with core BLUE-stream mechanisms (cGAS-STING, mitochondrial morphology/MAVS, VDAC1-adjacent apoptosis) relevant to SAMHD1 interferonopathy, but the retinal/ocular context and viral immunoevasion framing are tangential to the family's haploinsufficiency syndrome.
DOI: 10.1016/j.exer.2026.111009

JAK inhibition in PD-1 immunotherapy and tumor microenvironment (from Oncology/Immuno-oncology)
Ziyuan Liu; Jiaqi Liu; Hongyu Chu; Zhuming Lu; Shengshan Xu — Frontiers in Immunology 2026
Score: 5/10 | Pathways: JAK-STAT, treatment-target, other

This review covers JAK/STAT signaling and JAK inhibitors (baricitinib, ruxolitinib class) in the tumor microenvironment, which are directly relevant as treatment targets for the SAMHD1 interferonopathy (IFN-I → JAK-STAT1/2 → ISG15 → mitophagy block), but the paper's focus is on cancer immunotherapy resistance rather than the interferonopathy or mitochondrial mechanisms central to SAMHD1 haploinsufficiency, making it an indirect therapeutic connection.
DOI: 10.3389/fimmu.2026.1790936

Dysregulated dsRNA sensor signaling and viral infection during onset of pediatric autoimmune interferonopathy (from Pediatric rheumatology/myology)
MOREAU, T. R.; AQUINO, Y.; ZHU, Y. Y.; BONDET, V.; ALBERT-VEGA, C.; DONNADIEU, F — bioRxiv (preprint) 2026
Score: 5/10 | Pathways: JAK-STAT, AGS-spectrum, ME-CFS, cGAS-STING, clinical-phenotype, other

This paper demonstrates SARS-CoV-2 and RNA viral triggers driving dysregulated IFN-I/MDA5 signaling with myeloid ISG enrichment in pediatric autoimmune interferonopathy (JDM), which is mechanistically adjacent to the SAMHD1 haploinsufficiency model—particularly the viral trigger hypothesis (proband's adenovirus/SARS-CoV-2 onset), IFN-I loop amplification, and JAK-STAT pathway dysregulation—but does not address SAMHD1, cGAS-STING, VDAC1, mtDNA, or the specific dNTP-driven mechanism.
DOI: 10.64898/2026.05.27.728148

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases. (from cell biology / molecular pharmacology)
Borlepawar Ankush; Neu Marco; Ma Ziqi; Deshpande Anushka; Bühringer Hannah — 2026
Score: 4/10 | Pathways: mTOR-lysosomal, ISG15-mitophagy, NLRP3, other

This broad proteostasis review tangentially touches autophagy-mitophagy, ubiquitin-proteasome, and lysosomal pathways relevant to the ISG15-mitophagy block and NLRP3 inflammasome axes in the disease model, but contains no specific focus on SAMHD1, cGAS-STING, interferonopathy, or the core molecular players driving the convergent interferon-mitochondrial syndrome.
DOI: 10.1038/s41392-026-02714-4

Association Between Type I Interferonopathies and the Development of Cutaneous Sarcoidosis, Morphea, Lichen Planus and Granuloma Annulare: A Retrospective Cohort Study. (from Dermatology)
Block Brandon; Mehta Jaanvi; Soto-Canetti Gabriela; Tang Alice; Spingler Riley — 2026
Score: 4/10 | Pathways: JAK-STAT, AGS-spectrum, clinical-phenotype, other

This paper documents clinical associations between IFN-I-driven systemic diseases and specific autoimmune dermatoses (LP, morphea, CS, GA), confirming that chronic type I interferonopathy states predispose to these skin conditions, which is peripherally relevant as downstream phenotypic consequences of the same JAK-STAT/IFN-I axis central to SAMHD1 haploinsufficiency, but provides no mechanistic insight into cGAS-STING, NLRP3, VDAC1, or SAMHD1-specific pathways.
DOI: 10.1111/exd.70295

Coexisting ADAR and TSHB Mutations in an Infant With Retinal Detachment and Transient Cardiomyopathy. (from Neonatology/Pediatric Genetics)
Draidi Tamer; Khalil Mohammad; Kabaha Abed; Zuriqi Rafat; Masu'd Mohammad — 2026
Score: 4/10 | Pathways: AGS-spectrum, cGAS-STING, clinical-phenotype

This case documents ADAR-related AGS6, a type I interferonopathy sharing the AGS-spectrum with SAMHD1-related disease, but involves a different gene (ADAR), a distinct molecular mechanism (RNA editing failure rather than dNTPase/cGAS-STING), and the clinical novelty is the co-occurring TSHB mutation; the connection to SAMHD1 haploinsufficiency pathways is only via the broad interferonopathy/AGS diagnostic category.
DOI: 10.1155/crie/5534847

NF-κB signaling in osteoarthritis: integrating mechanical stress, innate immunity, and cartilage degeneration (from Rheumatology/Orthopedics)
Peng Wan; Yimin Zheng — Frontiers in Immunology 2026
Score: 4/10 | Pathways: NLRP3, VDAC1, POLG-mtDNA, urate-NLRP3, other

This OA review touches on NF-κB as a hub integrating mitochondrial dysfunction-associated DNA sensing (obliquely referencing cGAS-STING/NLRP3 pathways) and DAMP-driven innate immune circuits that overlap mechanistically with the SAMHD1 interferonopathy framework, but remains disease-context-specific to cartilage degeneration with no direct relevance to SAMHD1, type I interferon, ISG15-mitophagy, or the family phenotype cluster.
DOI: 10.3389/fimmu.2026.1842443

Identification and diagnostic potential of pyroptosis-related genes in endometriosis: A novel bioinformatics analysis and validation. (from Gynecology/reproductive medicine)
Wang Li; Teng Piaopiao; Chen Jiawen; Ding Caiyun; Luo Xianchen — 2026
Score: 3/10 | Pathways: NLRP3, clinical-phenotype, other

This paper investigates pyroptosis-related genes in endometriosis with some NLRP3/inflammasome relevance and touches on a gynecologic inflammatory condition, but the identified gene signatures (KIF13B, BAG6, MYO5A, HEATR2) have no direct connection to SAMHD1 pathways, cGAS-STING, or the core interferon-mitochondrial mechanism, making this only tangentially relevant via the shared pyroptosis/inflammasome biology and the family's endometrial carcinoma phenotype.
DOI: 10.1371/journal.pone.0350751

A designed peptide disrupting viral protease cleavage restores cGAS-DNA phase separation and type I interferon responses. (from veterinary virology / antiviral therapeutics)
Yin Hongyan; Zhao Zhenchao; Wang Haiwei; Li Xin — 2026
Score: 3/10 | Pathways: cGAS-STING, NLRP3, other

While the paper involves cGAS-DNA phase separation and innate immune signaling (cGAS-STING pathway) relevant to the disease mechanism, the context is entirely viral (SVV 3C protease in porcine systems) and addresses antiviral peptide inhibition rather than constitutive interferonopathy or SAMHD1-related pathology, making the connection tangential at best.
DOI: 10.1371/journal.ppat.1014291

Mechanisms by Which Exercise Delays Brain Aging Through Regulation of the Mitochondrial Quality Control System. (from Exercise physiology / sports medicine / neuroscience)
Zhu Xinyi; Shi Lei; Dong Yahong; Sun Yingjie; Jin Qiguan — 2026
Score: 3/10 | Pathways: mTOR-lysosomal, ISG15-mitophagy, other

This review covers mitochondrial quality control (biogenesis via PGC-1α/AMPK/SIRT1, mitophagy via PINK1/Parkin/mTOR, dynamics via Drp1) which are downstream components of the RED and PURPLE streams, but the paper is entirely focused on exercise as an intervention for brain aging with no connection to SAMHD1, interferonopathy, cGAS-STING, NLRP3, or the specific pathological context of this family.
DOI: 10.3390/biology15110854

The Role of MicroRNAs Carried by Extracellular Vesicles in Tumorigenesis Through Reprogramming the Mitochondrial Information Processing System. (from Oncology/Cancer Biology)
Ghosh-Mitra Arpita; Patel Mansi; Das Samarjit — 2026
Score: 3/10 | Pathways: VDAC1, POLG-mtDNA, mTOR-lysosomal, other

This review covers EV-miRNA reprogramming of mitochondrial dynamics, fission/fusion, and intrinsic apoptosis in tumorigenesis, touching peripherally on mitochondrial dysfunction and immune regulation relevant to the disease mechanism, but does not address SAMHD1, cGAS-STING, NLRP3, ISG15, interferonopathy, or any direct pathway component with meaningful specificity.
DOI: 10.3390/ijms27115112

Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics. (from hepatology-nephrology-cardiology (fibrosis))
Feng Yourong; Zhang Xudong; Wang Xin Joy; Chen Chen — 2026
Score: 3/10 | Pathways: IRF7-metabolic, mTOR-lysosomal, other

This review covers metabolic reprogramming in fibrosis (Warburg effect, glycolysis, lipid metabolism) with some overlap in downstream metabolic consequences of mitochondrial dysfunction and NF-kB/inflammatory signaling, but does not address cGAS-STING, NLRP3, SAMHD1, interferonopathy, or the core pathways driving the A565T syndrome, making the connection tangential.
DOI: 10.1186/s43556-026-00490-9

Clonal lineage tracing of innate immune cells in human cancer. (from Oncology/Tumor Immunology)
Vincent Liu; Katalin D. Sandor; Patrick K. Yan; Zhuang Miao; Yajie Yin — Cancer cell 2026
Score: 3/10 | Pathways: POLG-mtDNA, other

While this paper uses somatic mtDNA mutations as lineage tracing barcodes to study innate immune clonal dynamics in the tumor microenvironment, its use of mtDNA is purely as a neutral genetic marker rather than addressing any mechanistic pathway relevant to SAMHD1 haploinsufficiency, cGAS-STING, NLRP3, or mitochondrial dysfunction in the disease context.
DOI: 10.1016/j.ccell.2026.05.006

Effect of nanobody-STING agonists on the tumor microenvironment and adoptive cell therapy for solid tumors. (from Oncology/Immunotherapy)
Neil C. Chada; Alex Lee; Hailey Jane Frank; Dawn K. Oh; Hannah Ki — Journal of Clinical Oncology 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target, other

This paper involves STING pathway activation but purely in the context of tumor immunotherapy (adoptive cell therapy for solid tumors), with no mechanistic connection to SAMHD1 haploinsufficiency, interferonopathy, mitochondrial dysfunction, or the family phenotype constellation; the STING agonism here is an oncologic tool rather than an exploration of pathological constitutive cGAS-STING activation.
DOI: 10.1200/jco.2026.44.16_suppl.e14601

Abstract LB415: Nanobody:STING agonists reprogram the tumor microenvironment and improve adoptive cell therapy for solid tumors (from Oncology/Immuno-oncology)
Neil C. Chada; Alex Lee; Hailey Jane Frank; Dawn K. Oh; Hannah Ki — Cancer Research 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target, other

While this paper involves STING pathway activation, it focuses on a nanobody-based tumor immunotherapy platform for solid tumors rather than any aspect of SAMHD1 haploinsufficiency, interferonopathy, or the downstream mitochondrial/inflammasome mechanisms relevant to the disease profile; STING is used here as a pharmacological target to enhance adoptive cell therapy, not in the context of constitutive cGAS-STING activation from mtDNA escape or SAMHD1 dysfunction.
DOI: 10.1158/1538-7445.am2026-lb415

Pathway Coverage This Week

  • other: 36 papers
  • cGAS-STING: 30 papers
  • NLRP3: 23 papers
  • POLG-mtDNA: 23 papers
  • VDAC1: 20 papers
  • treatment-target: 16 papers
  • ISG15-mitophagy: 15 papers
  • ME-CFS: 12 papers
  • JAK-STAT: 7 papers
  • clinical-phenotype: 6 papers
  • mTOR-lysosomal: 6 papers
  • dNTPase: 5 papers
  • AGS-spectrum: 4 papers
  • IRF7-metabolic: 3 papers
  • pregnancy-fetal: 1 papers
  • urate-NLRP3: 1 papers

SAMHD1 Research Digest — 2026-06-07

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 21 papers evaluated | 9 high-relevance (≥7) | 6 medium (5–6) | 6 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis. (from Mitochondrial disease / Genetics)
Szabo Marton; Lagos Daniel; Cross Emily; Collier Jack J; Horvath Rita — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, NLRP3, POLG-mtDNA, ISG15-mitophagy, JAK-STAT, AGS-spectrum, ME-CFS, treatment-target, clinical-phenotype

This review directly covers the mechanistic chain central to SAMHD1 A565T pathogenesis—mtDNA release via mitochondrial membrane integrity loss (VDAC1), cGAS-STING activation, type I interferon/JAK-STAT signaling, and NLRP3 inflammasome engagement in primary mitochondrial diseases—and discusses therapeutic implications including cGAS-STING and NLRP3 inhibitors, making it highly relevant to all four mechanistic streams (PURPLE, BLUE, RED, GOLD) of the disease model.
DOI: 10.1093/brain/awag037

VDAC1 mediates LPS-induced T cell inflammation via mtDNA release and cGAS-STING activation. (from Critical care / sepsis immunology)
Yuqian Ren; Zhu Guangyao; Yucai Zhang; Yun Cui; Jie Gu — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, NLRP3, treatment-target, ME-CFS

This paper directly demonstrates the VDAC1 oligomerization → mtDNA cytosolic release → cGAS-STING-TBK1 activation axis (the BLUE stream) in primary T cells, validates VBIT-12 as a pharmacological inhibitor of this pathway, and reports IL-18 elevation consistent with NLRP3 co-activation, making it highly mechanistically relevant to SAMHD1 haploinsufficiency pathophysiology where SAMHD1/VDAC1 interaction loss is proposed to drive the same cascade.
DOI: 10.1016/j.cellsig.2026.112642

Fingolimod increases cellular resistance to HIV-1 infection and limits viral reservoir size in peripheral CD4+ T-cells. (from Virology/HIV medicine)
Moraga Elisa; Climent Núria; Sánchez-Molina Alejandro; Vicens-Artés Sònia; Malen — 2026
Score: 7/10 | Pathways: dNTPase, treatment-target, ME-CFS, other

This paper directly demonstrates that SAMHD1 phosphorylation inhibition (via fingolimod) enhances dNTPase activity to restrict viral replication, providing mechanistic insight into how modulating SAMHD1 activity state — directly relevant to the haploinsufficiency context — affects dNTP pool dynamics and viral restriction, with fingolimod as a potential treatment modulator of the same SAMHD1 activity axis central to the disease mechanism.
DOI: 10.1371/journal.ppat.1014266

ALA-PDT Induces Apoptosis in HPV-transformed Cells through mtDNA Release-Mediated Activation of the cGAS-STING Pathway. (from Dermatology/photodynamic therapy)
Lei Shuangyi; Xu Rui; Deng Yuan; Feng Sining; Chen Yu — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, treatment-target

This paper directly demonstrates the mechanistic sequence of mtDNA cytosolic release → cGAS-STING activation → apoptosis (confirmed by ρ0 depletion experiments), which is the core BLUE stream of the SAMHD1 haploinsufficiency mechanism, and pharmacological STING inhibition as a therapeutic target closely parallels the cGAS/STING inhibitor interventions (e.g., IMSB301) relevant to this disease.
DOI: 10.1016/j.pdpdt.2026.105534

Expanding roles of cGAS-STING signaling in neuroinflammation. (from Neurology/Neuroscience)
Feng Weixi; Aikedan Abulimiti; Sinha Subhash C; Gan Li — 2026
Score: 7/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, AGS-spectrum, ME-CFS, treatment-target

This review directly covers the cGAS-STING pathway (BLUE stream core mechanism) in neuroinflammation including canonical IFN-I induction, noncanonical nuclear roles, glial activation, blood-brain barrier integrity, and pharmacological inhibitors targeting cGAS/STING—all highly relevant to the SAMHD1 A565T interferonopathy mechanism where VDAC1-mediated cytosolic mtDNA fragments activate cGAS→cGAMP→STING→IRF3→IFN-I, and to the neurological phenotypes (AuDHD, ME/CFS, potential neurodegeneration) in the proband and family.
DOI: 10.1172/jci204550

Autoinflammatory syndromes of STING and TREX1 dysfunction. (from rare disease / genetics)
Park Debby J; Jones Kate M; Anderson Jessica B; Finck Amanda V; Miner Jonathan J — 2026
Score: 7/10 | Pathways: cGAS-STING, AGS-spectrum, dNTPase, treatment-target, clinical-phenotype

This review directly covers the cGAS-STING axis and its negative regulation by DNA-degrading enzymes (TREX1 paralleling SAMHD1's dNTPase role), STING gain-of-function vasculopathy, Aicardi-Goutières spectrum interferonopathies, and first-in-class small molecule therapeutics targeting this pathway—all directly mechanistically relevant to SAMHD1 haploinsufficiency-driven IFN-I overactivation via the BLUE stream (VDAC1→cGAS→STING→IRF3), though SAMHD1 itself is not discussed.
DOI: 10.1172/jci204549

Aspartate deficiency amplifies cGAS-STING signaling in antitumor immunity. (from Oncology/tumor immunology)
Liao Yuheng; Wang Hanze; Liu Hengxin; Chen Xi; Sun Renqiang — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, JAK-STAT, dNTPase, treatment-target

This paper directly illuminates a mechanistic link between nucleotide pool imbalance (aspartate/pyrimidine depletion causing mtDNA replication stress and DSBs → cytosolic mtDNA release → cGAS-STING → IRF3 → type I IFN amplification via ZBP1 feedback loop) that mirrors the SAMHD1 haploinsufficiency mechanism where dNTP pool expansion (especially dGTP) perturbs mtDNA replication via POLG stalling and drives cGAS-STING-mediated interferonopathy — the novel ZBP1/RIPK1/3 positive feedback loop sustaining IRF3 phosphorylation is a clinically important amplification mechanism not previously mapped in the SAMHD1 disease model.
DOI: 10.1172/jci199716

Fueling the fire: aspartate deficiency primes and fuels STING activation. (from Oncology/tumor immunology)
Jiang Haitao; Wang Wenyan; Fu Yang-Xin — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, dNTPase, ME-CFS, treatment-target

This paper directly addresses cGAS-STING pathway activation via mtDNA stress driven by nucleotide pool disruption (aspartate deficiency → pyrimidine depletion → mtDNA stress), which is mechanistically parallel to SAMHD1 haploinsufficiency causing dNTP pool imbalance → mtDNA stress → cGAS-STING activation, and introduces ZBP1/RIPK1/3 as a feed-forward amplifier of STING signaling relevant to understanding why interferonopathy is self-sustaining in this family.
DOI: 10.1172/jci206431

Mitochondrial protein COXFA4L3 (C15ORF48) confers resistance to DNA-damaging anticancer agents by repressing mitochondrial DNA damage responses. (from Oncology/Cancer Biology)
Takakura Yuki; Kawamura Seika; Hashiguchi Yui; Yamanaka Manami; Kurihara Yasuyuk — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, treatment-target

This paper directly demonstrates the mtDNA damage → cytosolic mtDNA release via mPTP → cGAS-STING activation axis that is central to the BLUE stream of SAMHD1 haploinsufficiency pathophysiology, specifically showing that mtDNA damage and mPTP-mediated cytosolic release drives cGAS-STING-dependent cell death, with COXFA4L3 as a novel repressor of this pathway—directly relevant to understanding how SAMHD1's interaction with VDAC1/mPTP components leads to chronic IFN-I signaling.
DOI: 10.1038/s41598-026-54548-3

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

GSDME-Mediated Pyroptosis and the mtDNA-cGAS-STING Pathway Drive Deoxynivalenol-Induced Porcine Intestinal Inflammatory Injury. (from Veterinary/Food toxicology and gastroenterology)
Zhou Fenfen; Li Jie; Li Mingxuan; Guo Chongwen; Mao Xiaoxiao — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, other

This paper directly demonstrates the mechanistic sequence of mitochondrial membrane permeabilization → cytosolic mtDNA release → cGAS-STING activation driving chronic intestinal inflammation, which mirrors the BLUE pathway (VDAC1 macropore → mtDNA escape → cGAS-STING) central to SAMHD1 haploinsufficiency, though the trigger (GSDME/caspase-3 pyroptosis from mycotoxin) is distinct from SAMHD1-driven VDAC1 dysregulation.
DOI: 10.1021/acs.jafc.6c01535

Interstitial lung disease and the STING pathway. (from Pulmonology)
Velu Prasad Palani; Zhu Gaofeng; Mackenzie Karen J — 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, AGS-spectrum, treatment-target, clinical-phenotype

This review directly covers the STING pathway in ILD, including SAVI and COPA syndrome which are type I interferonopathies mechanistically overlapping with SAMHD1 haploinsufficiency via cGAS-STING-IRF3 signaling, and discusses STING-targeted therapeutics relevant to Loop A of the disease mechanism, though it does not address SAMHD1, mtDNA, VDAC1, or the specific family phenotype.
DOI: 10.1172/jci204544

An Engineered Microbial Nanohybrid for Enhanced Ferroptosis Immunotherapy via Hypoxia-Responsive Hydrogen Sulfide Generation and Mitophagy Inhibition. (from Oncology/Nanomedicine)
Li Yuewei; Xu Shujing; Wang Guocheng; Song Zhangzhi; Zhang Shuqi — 2026
Score: 5/10 | Pathways: cGAS-STING, POLG-mtDNA, ISG15-mitophagy, BIK-cancer, treatment-target

The paper demonstrates mechanistic relevance to the disease model—specifically cytosolic mtDNA accumulation activating cGAS-STING and deliberate mitophagy inhibition (Mdivi-1) to sustain that signal—but is framed entirely as an oncology ferroptosis immunotherapy strategy in a murine mammary carcinoma model, with no connection to SAMHD1, haploinsufficiency, or the interferonopathy syndrome; the mechanistic insights into mtDNA–cGAS–STING amplification via mitophagy blockade are indirectly informative for understanding the RED/BLUE loop intersection in the disease mechanism.
DOI: 10.1021/acsnano.6c06383

Mitophagy in cisplatin-induced kidney injury: regulatory mechanisms and therapeutic targets. (from nephrology/oncology)
Yuan Cheng; Jiang Jinzhou; Ji Jinxing; Ni Lihua — 2026
Score: 5/10 | Pathways: NLRP3, ISG15-mitophagy, POLG-mtDNA, mTOR-lysosomal, other

This review covers PINK1/Parkin-dependent mitophagy, pyroptosis/NLRP3 inflammasome, and mitochondrial quality control mechanisms that are directly relevant to the RED-stream ISGylation-mediated mitophagy block and NLRP3 activation central to the disease model, but the cisplatin-AKI context is clinically unrelated and the paper does not address cGAS-STING, SAMHD1, or type I interferonopathy.
DOI: 10.1080/07853890.2026.2672141

Mitochondrial dysfunction in neurodegenerative disorders: mechanisms and therapeutic advances. (from Neurology/neurodegeneration)
Tong Yan; He Jing Na; Zhou Linbin; Zhang Jiaxin; Ho Bo Man — 2026
Score: 5/10 | Pathways: POLG-mtDNA, ISG15-mitophagy, VDAC1, mTOR-lysosomal, treatment-target, other

This review covers mitochondrial dynamics, quality control (mitophagy), oxidative phosphorylation defects, and mtDNA integrity—all mechanistically central to the PURPLE and RED streams of the SAMHD1 haploinsufficiency model—but does not engage with cGAS-STING, interferonopathy, NLRP3, or SAMHD1 itself, making it background context rather than directly actionable evidence.
DOI: 10.1186/s43556-026-00480-x

PRKN Ser131 phosphorylation promotes cigarette smoke-induced mitophagy impairment and epithelial cell senescence via MKK3/p38 MAPK activation: An in vitro and in vivo study. (from Pulmonology/COPD)
Hu Yajie; Liu Jianyu; Zhang Mengyu; Qu Jiajia; Hao Wenqiang — 2026
Score: 5/10 | Pathways: ISG15-mitophagy, other

This paper directly investigates Parkin (PRKN)/PINK1-dependent mitophagy impairment via a phosphorylation-mediated block, which is directly relevant to the RED stream where ISGylation of PINK1/Parkin blocks mitophagy, but the mechanism here is MKK3/p38 MAPK-driven rather than ISG15/interferonopathy-driven, making it an adjacent mechanistic parallel rather than a core pathway contribution.
DOI: 10.18332/tid/218816

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Metabolic dysfunction-associated steatotic liver disease: pathogenesis and novel treatment options. (from hepatology)
Ren Ruizhe; Liang Xiao; Wei Xiyang — 2026
Score: 4/10 | Pathways: NLRP3, IRF7-metabolic, mTOR-lysosomal, urate-NLRP3, other

MASLD review touches on mitochondrial dysfunction, inflammasome/NLRP3 activation, and hepatic steatosis which are family phenotype-adjacent (hepatic steatosis listed explicitly, cholecystectomy clustering), but does not engage cGAS-STING, SAMHD1, ISG15, VDAC1, or interferonopathy mechanisms that would make it mechanistically relevant to the disease profile.
DOI: 10.1186/s43556-026-00486-5

A genomic structural equation modelling analysis of the shared genetic architecture of the aging spine. (from Orthopedic genetics / musculoskeletal genomics)
Chen Jianquan; Zhong Xingjie; Li Liping; Feng Peiyun; Duan Xiuping — 2026
Score: 3/10 | Pathways: dNTPase, other

SAMHD1 appears as a GWAS/TWAS susceptibility gene for aging spine traits (lumbar spinal stenosis, disc degeneration, sciatica) via genomic stability pathways, but the paper treats it purely as a statistical genomic signal without any mechanistic investigation of dNTPase function, interferonopathy, or the SAMHD1 p.A565T variant, making it tangentially relevant at best.
DOI: 10.1007/s00586-026-10039-7

Highly Efficient Lentiviral Transduction of Human iPSC-Derived Microglia and Macrophages (from Neuroscience/cell biology methods)
Goberdhan Srilakshmi; Czubala Magdalena; Thomas Sophie; Taylor Philip; Connor-Ro — 2026
Score: 3/10 | Pathways: dNTPase, other

This paper mentions SAMHD1 only as a lentiviral restriction factor in myeloid cells that is removed via VPX to improve transduction efficiency in iPSC-derived microglia, providing no mechanistic insight into SAMHD1 haploinsufficiency, dNTPase function, or any of the core interferon-mitochondrial pathways relevant to the A565T variant.
DOI: 10.64898/2026.05.23.727402

Insights into the therapeutic strategies for aging and aging-associated diseases. (from Geroscience/longevity medicine)
Dong Ruifang; Wu Qiming; Kan Juntao; Fu Caili; Sorrentino Vincenzo — 2026
Score: 3/10 | Pathways: mTOR-lysosomal, NLRP3, ISG15-mitophagy, other

This broad aging review touches on mitochondrial impairment, cellular senescence, autophagy (rapamycin/mTOR), and SASP—mechanisms that partially overlap with the SAMHD1 interferonopathy-mitochondrial cascade—but contains no direct engagement with cGAS-STING, NLRP3 inflammasome, VDAC1, ISG15, or SAMHD1, making it only tangentially relevant as background context.
DOI: 10.1038/s41392-026-02662-z

Nanozymes for Bone Regeneration: Mechanistic Insights into Immune and Metabolic Microenvironment Modulation. (from Biomaterials/Orthopedic tissue engineering)
Wang Yue; Song Meiyuan; Chen Shumeng; He Yang; Chen Shuxuan — 2026
Score: 3/10 | Pathways: NLRP3, other

This nanozyme review touches on NLRP3/NF-κB suppression and mitochondrial function restoration in the context of bone regeneration, which are peripheral overlaps with the disease mechanism, but the paper is fundamentally about biomaterial engineering for orthopedic repair with no connection to SAMHD1, interferonopathy, dNTP biology, or the family phenotype.
DOI: 10.2147/ijn.s607165

The homozygous founder Psmb8 variant of Nakajo-Nishimura syndrome/proteasome-associated autoinflammatory syndrome causes panniculitis-associated lipoatrophy and a shortened lifespan in mice. (from Rare disease / autoinflammatory immunology)
Hara Tomoyuki; Kinoshita Akira; Hamazaki Jun; Hemmi Hiroaki; Kato Takashi — 2026
Score: 3/10 | Pathways: NLRP3, JAK-STAT, AGS-spectrum, clinical-phenotype, other

This paper describes a proteasome-dysfunction autoinflammatory syndrome (NNS/PRAAS) driven by PSMB8 variants, which causes type I interferonopathy features (periodic fever, lipoatrophy, cytokine activation) via a proteasome-ubiquitin pathway mechanistically distinct from the SAMHD1/cGAS-STING/NLRP3 axes central to SAMHD1 A565T haploinsufficiency, making it a tangential interferonopathy model with limited direct pathway overlap.
DOI: 10.1038/s41598-026-51190-x

Pathway Coverage This Week

  • treatment-target: 12 papers
  • cGAS-STING: 11 papers
  • other: 11 papers
  • POLG-mtDNA: 9 papers
  • NLRP3: 8 papers
  • VDAC1: 6 papers
  • ISG15-mitophagy: 6 papers
  • dNTPase: 6 papers
  • JAK-STAT: 5 papers
  • AGS-spectrum: 5 papers
  • ME-CFS: 5 papers
  • clinical-phenotype: 4 papers
  • mTOR-lysosomal: 4 papers
  • IRF7-metabolic: 3 papers
  • BIK-cancer: 1 papers
  • urate-NLRP3: 1 papers

SAMHD1 Research Digest — 2026-05-31

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 44 papers evaluated | 24 high-relevance (≥7) | 9 medium (5–6) | 11 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Rab26 Mitigates Ferroptosis in Airway Epithelium Induced by Cigarette Smoke Through Suppression of VDAC1 Oligomerization-Mediated cGAS-STING Activation. (from Pulmonology/COPD)
Tian Xin; Zhang Wen; You Zaichun; Mao Yang; Huang Qiuhong — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target

This paper directly demonstrates the VDAC1 oligomerization → cytosolic mtDNA release → cGAS-STING activation axis (the BLUE stream of the SAMHD1 haploinsufficiency mechanism), providing novel molecular detail on how VDAC1 macropore formation drives cGAS-STING hyperactivation, and validates STING inhibition as a pharmacological rescue—highly relevant to the SAMHD1/VDAC1 interaction loss mechanism in this disease.
DOI: 10.1016/j.freeradbiomed.2026.05.315

Glutathione peroxidase 3 preserves hepatocyte mitochondrial quality control to enhance macrophage pro-regenerative phenotype during liver regeneration. (from Hepatology)
Wang Yuechen; Xu Jian; Zhu Zeyu; Zhang Ye; Hu Haoran — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, JAK-STAT, POLG-mtDNA, treatment-target

This paper directly demonstrates the mechanistic axis of VDAC1 oligomerization → mtDNA release → cGAS-STING activation → type I interferon overproduction that constitutes the BLUE stream of the SAMHD1 A565T pathomechanism, with the added finding that STING hyperactivation suppresses regenerative signaling — providing a novel hepatology context and a GPX3-based therapeutic angle relevant to the family's hepatic phenotype (cholecystectomy clustering, hepatic steatosis).
DOI: 10.1002/ctm2.70695

Pathogenic variants in the autophagy-tethering factor EPG5 drive neurodegeneration through mitochondrial dysfunction and innate immune activation. (from Neurology/rare disease (Vici syndrome/EPG5))
Singh Kritarth; Dafsari Hormos Salimi; Gillham Olivia; Chi Haoyu; Mandzhukova Iv — 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, POLG-mtDNA, mTOR-lysosomal, treatment-target

This paper directly demonstrates the mechanistic cascade central to the SAMHD1 A565T syndrome: impaired mitophagy → mitochondrial bioenergetic dysfunction → mtDNA release → cGAS-STING innate immune activation, with pharmacological rescue by mPTP or STING inhibition, precisely mirroring the BLUE and RED pathway loops in the disease mechanism, and providing therapeutic target validation highly relevant to this interferonopathy.
DOI: 10.1038/s41467-026-73538-7

Self-assembled nanoparticles from Xiexin Decoction attenuate ulcerative colitis by targeting VDAC1-Mediated NLRP3 inflammasome activation (from Nanomedicine/Traditional Chinese Medicine pharmacology)
Zheng Chu; Tong Yang; Ying Zhang; Qianru Zhu; Dawei Wang — Materials Today Bio 2026
Score: 8/10 | Pathways: VDAC1, NLRP3, cGAS-STING, POLG-mtDNA, treatment-target

This paper directly demonstrates that VDAC1 oligomerization drives cytosolic oxidized mtDNA release → NLRP3 inflammasome activation in macrophages, precisely the BLUE+PURPLE mechanistic axis of SAMHD1 haploinsufficiency, and identifies berberine as a functional VDAC1 inhibitor that blocks this pathway—providing a directly actionable treatment target for the convergent interferon-mitochondrial syndrome described.
DOI: 10.1016/j.mtbio.2026.103078

TH5487 specifically targets NLRP3 in FCAS patients resistant to MCC950 (from chemical biology / rare autoinflammatory disease (FCAS))
Angela Lackner; Sofia I. Picucci; Wenjing Jiang; Janset Onyuru; Melissa Campos — Communications Biology 2026
Score: 8/10 | Pathways: NLRP3, POLG-mtDNA, cGAS-STING, treatment-target, ME-CFS

This paper directly addresses NLRP3 inflammasome regulation via oxidized mitochondrial DNA sensing (cryo-EM showing NLRP3-mtDNA association), introduces a novel druggable mechanism (hOGG1 inhibition via TH5487) effective where MCC950 fails, and notably reports that these inhibitors simultaneously reduce IL-1β while increasing type I interferon responses—directly relevant to the PURPLE stream (ox-mtDNA → NLRP3) and the convergent interferon-mitochondrial syndrome mechanism, with clear treatment implications for MCC950-resistant NLRP3 activation in this haploinsufficiency context.
DOI: 10.1038/s42003-026-10008-2

Oxidized mtDNA Contributes to Pulmonary Inflammation and Fibrosis in Bleomycin‐Induced Lung Injury (from Pulmonology/fibrosis)
Ye Mao; Xinyu Tian; Jiayuan Ai; Xiaoting Zhou; Yanghong Ni — MedComm 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, other

This paper directly demonstrates that oxidized mtDNA (the exact molecular species generated by POLG stalling in the PURPLE pathway) activates both cGAS-STING and NLRP3 downstream to drive inflammation and fibrosis, with knockout mouse validation of both pathways — mechanistically mirroring the BLUE and GOLD/PURPLE loops central to the SAMHD1 A565T syndrome.
DOI: 10.1002/mco2.70664

Human Immunodeficiency Virus Type 2 Vpx-mediated Degradation of TASOR Activates Innate Immune Sensing of Nucleic Acids in Infected Cells. (from Virology/Retrovirology)
Hanson Heather M; Damkot Madeline R; Mansky Louis M — 2026
Score: 7/10 | Pathways: cGAS-STING, dNTPase, JAK-STAT, AGS-spectrum, ME-CFS

This paper directly demonstrates that SAMHD1 degradation by Vpx elevates dNTP levels and that a parallel Vpx function (TASOR/HUSH degradation) activates cGAS-STING and MAVS-mediated ISG induction in monocytic cells, providing mechanistic context for how SAMHD1 haploinsufficiency combined with viral triggers (e.g., adenovirus/SARS-CoV-2) could synergize to amplify the cGAS-STING-ISG axis central to the family's interferonopathy.
DOI: 10.1016/j.jmb.2026.169879

PLSCR3 Deficiency Triggers mtDNA-Driven cGAS-STING Activation to Potentiate Antitumor Immunity in Colorectal Cancer. (from Oncology (colorectal cancer immunotherapy))
Ling Limian; Wu Jingyu; Bao Lei; Liu Zhaohui; Deng Qun — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, ISG15-mitophagy, JAK-STAT, BIK-cancer

This paper directly demonstrates that mitochondrial inner membrane disruption (via PLSCR3 deficiency) causes cytosolic mtDNA leakage activating cGAS-STING → IFNβ/CXCL10/ISG upregulation with functional immune consequences — precisely the BLUE stream mechanism in the SAMHD1 A565T model (VDAC1/mtDNA escape → cGAS → cGAMP → STING → IRF3 → IFN-I), and identifies PLSCR3 as a novel endogenous restraint on mtDNA release at the IMM, offering a new regulatory node adjacent to the disease mechanism.
DOI: 10.1155/humu/8545428

XBP1-mediated mitochondrial damage activates the mtDNA/STING/NLRP3 pathway to delay diabetic wound healing. (from Wound healing / diabetology)
Yi Min; Yan Wei; Tu Liying; Ni Tianyi; Zhang Qian — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target

This paper directly demonstrates the mtDNA → cGAS/STING → NLRP3 inflammatory cascade activated by mitochondrial damage in macrophages — the exact BLUE+PURPLE convergent pathway central to the SAMHD1 A565T mechanism — with XBP1 as an upstream trigger and pharmacological inhibition as a treatment strategy, providing mechanistic and therapeutic insight highly relevant to the disease model.
DOI: 10.1097/cm9.0000000000004113

Mitochondrial drivers of stem cell aging and inflammaging. (from Stem cell biology / geroscience)
Bautista Jhommara; López-Cortés Andrés — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, ISG15-mitophagy, mTOR-lysosomal, ME-CFS, treatment-target, other

This review directly covers the core mechanistic streams of the SAMHD1 syndrome—mtDNA damage activating cGAS-STING, mitophagy failure (MQC erosion including fission-fusion and mitophagy), mtDAMP-driven inflammaging, and NAD⁺/sirtuin collapse—while also evaluating mitophagy enhancers and mitochondrial quality control as therapeutic targets, all highly relevant to the RED and BLUE pathway loops and the chronic inflammatory tone seen in ME/CFS and interferonopathy contexts, though SAMHD1 is not mentioned.
DOI: 10.1038/s41514-026-00422-5

Mitochondrial flagella-like extensions (MitoFLARE) dysfunction triggers STING-mediated immune dysregulation in sepsis. (from critical care / sepsis biology)
Hong Weilong; Ma Ruiyan; Long Shiyun; Song Rui; Ren Shuang — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, other

This paper directly describes the mechanistic pathway from mitochondrial outer membrane rupture → cytosolic mtDNA release → cGAS-STING activation → inflammatory storm, which mirrors the BLUE stream of the SAMHD1 haploinsufficiency mechanism (VDAC1 macropore → mtDNA escape → cGAS-STING → IFN-I), and introduces novel intermediaries (MICOS-SAM complex disruption, mitoFLARE nanotube collapse, ER-mitochondrial contacts) that could explain how SAMHD1 loss of VDAC1 interaction accelerates outer membrane rupture and chronically activates cGAS-STING in a non-sepsis context.
DOI: 10.1038/s41467-026-73523-0

Mitochondrial Regulation of the NLRP3 Inflammasome in Diabetic Kidney Disease: From Mechanisms to Therapeutic Strategies (from Nephrology/Diabetology)
Xiangyun Chen; Zhenyu Wu; Kaiyan Yu; Juan Zhang; Hongjie Di — International Journal of Molecular Sciences 2026
Score: 7/10 | Pathways: NLRP3, POLG-mtDNA, VDAC1, urate-NLRP3, treatment-target

This review directly addresses the mitochondria–NLRP3 inflammasome axis including ox-mtDNA and mtROS as NLRP3 activators, which maps precisely onto the PURPLE and GOLD streams of the SAMHD1 A565T mechanism (POLG stalling → ox-mtDNA → NLRP3; urate-NLRP3), and evaluates therapeutic targeting strategies applicable to the family's inflammasome-driven pathology.
DOI: 10.3390/ijms27114819

Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies (from hepatology/transplant surgery)
Ruotong Shen; Peng An; Meng Chen; Ping Lu; Jingjing Yang — Journal of Translational Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target

This paper directly covers the core mechanistic triad—mtDNA escape → cGAS-STING activation → NLRP3 inflammasome/pyroptosis—plus mitochondrial quality control failure (mitophagy/fusion-fission/MDVs) that mirrors the PURPLE and BLUE loops in the SAMHD1 interferonopathy model, with explicit discussion of VDAC-mediated permeability, oxidized mtDNA as DAMP, and therapeutic intervention at each node (cGAS-STING inhibition, NLRP3 inhibition), making it highly mechanistically relevant even though the clinical context is hepatic IRI rather than SAMHD1 haploinsufficiency.
DOI: 10.1186/s12967-026-08155-5

Mitochondrial Dysfunction in the Inflammatory Process of Neurodegenerative Diseases (from Neurology/neurodegeneration)
Salvatore Nesci — Biomedicines 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, treatment-target, other

This review directly covers the mitochondrial dysfunction → oxidized mtDNA → cGAS-STING and NLRP3 inflammasome feed-forward loops that constitute the PURPLE and BLUE mechanistic streams of SAMHD1 haploinsufficiency, including respiratory supercomplex ROS generation, mtDNA damage-associated molecular pattern release, and therapeutic nodes targeting electron transport chain and mtDNA-sensing pathways, making it highly mechanistically relevant even without mentioning SAMHD1 itself.
DOI: 10.3390/biomedicines14030682

Mitochondrial Dysfunction in Acute Kidney Injury: Intersections Between Chemotherapy and Novel Cancer Immunotherapies (from Nephrology/Oncology)
Zaroon Zaroon; Carlotta D'Ambrosio; Filomena de Nigris — Biomolecules 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, treatment-target, other

This review directly covers cGAS-STING activation by mtDNA DAMPs and NLRP3 inflammasome engagement in the context of mitochondrial dysfunction, providing mechanistic overlap with the BLUE and PURPLE streams of the SAMHD1 interferonopathy model, and discusses mitochondrial-targeted therapeutics relevant to the treatment-target pathway.
DOI: 10.3390/biom16010120

BTNL2 Inhibits Pyroptosis in H37Ra-Infected Macrophages by Maintaining Mitochondrial Homeostasis (from Microbiology/Infectious Disease)
Yazhi Feng; Yiyao Liu; Guangxin Chen; Changxin Wu — Microorganisms 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA

This paper directly demonstrates the mechanistic convergence of mitochondrial damage → cytosolic mtDNA release → cGAS-STING hyperactivation → NLRP3 transcriptional upregulation → pyroptosis loop that is central to the BLUE and PURPLE streams of the SAMHD1 A565T disease mechanism, albeit in a BTNL2/mycobacterial infection context rather than SAMHD1 haploinsufficiency.
DOI: 10.3390/microorganisms14061188

Senegenin Attenuates LPS-Induced Neuroinflammation and Microglial Cell Death via Akt Phosphorylation and Suppression of cGAS-STING-NLRP3 Signaling: Network Pharmacology and Experimental Validation. (from Ethnopharmacology/Neuropharmacology)
Chandan Chauhan; R. Kaundal — Journal of ethnopharmacology 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, treatment-target, POLG-mtDNA, ME-CFS

This paper directly validates suppression of the cGAS-STING-TBK1-IRF3-IFN-β axis alongside NLRP3 inflammasome inhibition and mitochondrial protection (preserved Δψm, reduced mtDNA damage) by a single compound, making senegenin a potentially relevant therapeutic candidate for the convergent interferon-mitochondrial syndrome driven by SAMHD1 haploinsufficiency, though the context is LPS-driven neuroinflammation rather than SAMHD1 or dNTP-pool pathology.
DOI: 10.1016/j.jep.2026.121396

Atrazine increases hepatic inflammation and injury via endoplasmic reticulum (ER) stress mediated excessive formation of mitochondria-associated membranes (MAMs) and activation of the cGAS-STING pathway. (from Environmental toxicology/hepatology)
Zi-Jun Sun; Guanqi Shan; Hui Wan; Yu-xin Zhang; Zhi-Cheng Gao — Environmental pollution 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, clinical-phenotype, other

This paper directly demonstrates the mechanistic cascade of cytosolic mtDNA release → cGAS-STING activation → NLRP3 inflammasome assembly in a hepatic context, precisely mirroring the BLUE and PURPLE loops of the SAMHD1 haploinsufficiency mechanism, and additionally implicates mitochondria-associated membranes (MAMs) and mtROS as intermediaries, offering novel therapeutic targets (4-PBA, MitoQ) relevant to the convergent interferon-mitochondrial syndrome, while also connecting to the family phenotype of hepatic steatosis and inflammation.
DOI: 10.1016/j.envpol.2026.127959

The Autophagy–Inflammation Axis in Kawasaki Disease: Pathogenic Mechanisms and Translational Opportunities (from Pediatric cardiology/vasculitis)
Qiang Xu; Yali Wu; Yan Ding — Journal of Clinical Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, mTOR-lysosomal, POLG-mtDNA, treatment-target

This review directly describes the convergent mechanistic triad central to SAMHD1 haploinsufficiency pathology—defective mitophagy and lysosomal dysfunction causing mtDNA release that activates both NLRP3 inflammasome and cGAS-STING pathways driving vascular inflammation—and identifies rapamycin/metformin/resveratrol/urolithin A as therapeutic targets for this axis, providing translational relevance even though SAMHD1 is not mentioned.
DOI: 10.3390/jcm15103918

Understanding Dysfunctional Autophagy and Mitophagy in Inflammatory Cardiovascular Disease (from Cardiology)
Michael E. Kaiser; Toni-ann Lewis; M. Malekan; Manish A. Parikh; Gioia Turitto — Cardiology in Review 2026
Score: 7/10 | Pathways: NLRP3, VDAC1, ISG15-mitophagy, cGAS-STING, POLG-mtDNA, treatment-target, clinical-phenotype

This review directly covers the mechanistic triad central to the disease model—dysfunctional mitophagy (ISG15/MFN1/MFN2/PINK1-Parkin block), NLRP3 inflammasome hyperactivation (including pyroptosis and IL-1β/IL-18 cascades), and mtDNA leakage driving innate immune activation—within the cardiovascular disease context that is a relevant family phenotype, providing treatment-target framing for the RED and PURPLE pathway loops.
DOI: 10.1097/crd.0000000000001302

Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model (from Exercise physiology / rehabilitation medicine)
Hongjiao Jin; Yi An; Jingwei Huang; Tingting Luo; Xi Wu — Frontiers in Immunology 2026
Score: 7/10 | Pathways: NLRP3, POLG-mtDNA, ME-CFS, cGAS-STING, ISG15-mitophagy, other

This review directly addresses PEM pathophysiology in ME/CFS and Long COVID through the lens of mitochondrial dysfunction, mtDNA-DAMP activation of NLRP3, ROS overproduction, and disrupted metabolic-immune crosstalk—all core mechanistic streams of the SAMHD1 A565T interferonopathy model, making it highly relevant to the proband's post-viral ME/CFS phenotype even without direct SAMHD1 mention.
DOI: 10.3389/fimmu.2026.1774310

Conjugated bile acids facilitate cholangiocyte senescence to promote cholestatic liver diseases via STING signaling. (from Hepatology)
Guifang Fan; Xin Li; Yiran Li; Shuni Duan; Wenqing Qin — Journal of advanced research 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, clinical-phenotype, treatment-target

This paper directly demonstrates the mechanistic chain of mitochondrial permeability transition pore opening → oxidized mtDNA leakage → STING activation → SASP/inflammasome/pyroptosis in a hepatic cholestatic context, which precisely mirrors the BLUE and PURPLE pathway streams in the SAMHD1 disease model, and the cholecystectomy clustering family phenotype makes hepatobiliary STING activation a clinically actionable bridge.
DOI: 10.1016/j.jare.2026.03.020

Structural and Functional Alterations of MAMs and Their Immunomodulatory Roles in Sepsis‐Induced Lung Injury (from Critical care / pulmonology)
Yihao Wang; Jingran Yang; Xia Li — Journal of Immunology Research 2026
Score: 7/10 | Pathways: VDAC1, NLRP3, POLG-mtDNA, cGAS-STING, ISG15-mitophagy, treatment-target

This review directly addresses VDAC1 (a core player in the BLUE stream mtDNA escape pathway), MFN2 (targeted by ISGylation in the RED stream mitophagy block), NLRP3 inflammasome activation via mitochondrial dysfunction, and mtDNA release as inflammatory triggers—all mechanistically central to SAMHD1 haploinsufficiency pathophysiology, with therapeutic strategies (MFN2 upregulation, MAM integrity restoration) offering translatable treatment targets.
DOI: 10.1155/jimr/9888339

Abstract 6602: Venetoclax enhances radiation-induced anticancer immunity in breast cancer. (from Oncology/Radiation Biology)
E. Guilbaud; Ai Sato; Lorenzo Galluzzi — Cancer Research 2026
Score: 7/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, JAK-STAT, BIK-cancer, treatment-target

This paper directly characterizes the BAX/BAK→MOMP→cytosolic mtDNA→cGAS/STING→type I IFN axis and its antagonism by mitophagy (ATG5/ATG7-dependent), which is mechanistically identical to the BLUE and RED loops of the SAMHD1 A565T disease model, and Venetoclax (BCL2 inhibitor via BH3-only pathway) represents a pharmacological handle on the same MOMP/mtDNA-release/IFN amplification circuit relevant to the family's interferonopathy and cancer susceptibility phenotypes.
DOI: 10.1158/1538-7445.am2026-6602

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

Natural Product Treatment for Metabolic Dysfunction-Associated Steatotic Liver Disease: Targeted Mitochondrial Quality Control. (from Hepatology)
Liu Jing; Li Fuxing; Zeng Qianru; Hu Wenxiao; Yang Le — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, IRF7-metabolic, POLG-mtDNA, mTOR-lysosomal, treatment-target, clinical-phenotype

This review directly addresses hepatic steatosis (a family phenotype), mtDNA release activating cGAS-STING and TLR9, PINK1/Parkin-mediated mitophagy impairment, and PGC-1α biogenesis—all core pathways in the SAMHD1 haploinsufficiency mechanism—with pharmacological targeting implications, but does not address SAMHD1 or interferonopathy-driven liver disease specifically.
DOI: 10.2147/dddt.s610273

Toxoplasma gondii effector MAF1 blocks mouse AIM2 inflammasome activation by inhibiting mtDNA release. (from Infectious disease / parasitology)
Xiaoyu Zhao; Nadia Holness; Samantha L. Lempke; Lena Pernas; L. Newman — Journal of immunology 2026
Score: 6/10 | Pathways: NLRP3, POLG-mtDNA, cGAS-STING, other

This paper directly demonstrates that cytosolic mtDNA release activates the AIM2 and NLRP3 inflammasomes downstream of IFN-γ priming, mechanistically paralleling the PURPLE and BLUE streams in the SAMHD1 disease model where ox-mtDNA escape through VDAC1 macropores drives inflammasome activation, though the pathogen-specific MAF1/mitochondrial recruitment context is not directly relevant to SAMHD1 haploinsufficiency.
DOI: 10.1093/jimmun/vkaf360

Ag2Se quantum dots neurotoxicity: mitochondrial stress drives ferroptosis-dependent microglial inflammation (from Nanotoxicology/neurotoxicology)
Yongshuai Yao; Zhihui Wang; Chunhui Zhang; Xiaoquan Huang; T. Wei — Journal of Nanobiotechnology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, mTOR-lysosomal

This paper directly demonstrates the mechanistic chain of mtROS → mtDNA cytoplasmic leakage via mPTP (analogous to VDAC1 macropore) → STING activation → NLRP3 inflammasome in microglia, which closely mirrors the BLUE and PURPLE streams of the SAMHD1 A565T pathomechanism, though the trigger (Ag2Se QDs) is exogenous toxicity rather than dNTP pool expansion.
DOI: 10.1186/s12951-026-04322-4

Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives (from Mitochondrial biology / biochemistry)
Swarnali Basu; Rukshar Khan; Shiva Sharma; P. Prajapati; Veena Ammanathan — The Journal of Biological Chemistry 2026
Score: 6/10 | Pathways: NLRP3, POLG-mtDNA, cGAS-STING, mTOR-lysosomal, ME-CFS, treatment-target, other

This review directly addresses mitochondrial translation dysfunction as a driver of NLRP3 inflammasome activation, mtDNA/RNA release as DAMPs, mito-nuclear communication, and mTOR-regulated stress responses—all mechanistically downstream of the POLG-stalling and oxidized mtDNA accumulation predicted in the PURPLE and BLUE streams of the SAMHD1 haploinsufficiency model—but does not address SAMHD1, cGAS-STING, VDAC1, or ISG15 directly.
DOI: 10.1016/j.jbc.2026.111455

Targeting the NLRP3 Inflammasome in Atherosclerosis: A Review of Natural Products and Their Molecular Mechanisms (from Cardiology/Vascular Biology)
Su-Jin Bae; Hye-Min Seo; Si-Eon You; Junho H. Lee — International Journal of Molecular Sciences 2026
Score: 5/10 | Pathways: NLRP3, urate-NLRP3, mTOR-lysosomal, treatment-target, other

This review covers NLRP3 inflammasome biology (a core pathway in the GOLD and PURPLE streams of the disease mechanism) and details natural product inhibitors targeting NLRP3 priming, mitochondrial ROS, and autophagic flux restoration via AMPK/mTOR — all relevant to the convergent interferon-mitochondrial syndrome — but the context is atherosclerosis/ASCVD rather than interferonopathy or SAMHD1, and no direct mechanistic link to cGAS-STING, VDAC1, ISG15, or dNTPase is made.
DOI: 10.3390/ijms27083650

Recalibrating cell fate: targeting the mitochondrial signaling hub with natural active compounds to inhibit regulated cell death in diabetic kidney disease (from Nephrology/diabetic kidney disease)
Yinzhong Dai; Chenguang Wu; Jiaying Zheng; Keqin Zhao; Shimei Hua — Frontiers in Physiology 2026
Score: 5/10 | Pathways: NLRP3, VDAC1, POLG-mtDNA, mTOR-lysosomal, treatment-target, other

This paper covers NLRP3 inflammasome activation by cytosolic mtDNA leakage (via mitochondrial outer membrane permeabilization/VDAC), mitochondrial quality control failure, and regulated cell death crosstalk that are mechanistically parallel to the SAMHD1 haploinsufficiency disease model, but in a diabetic kidney context with no direct connection to SAMHD1, interferonopathy, or the specific molecular players of the family syndrome.
DOI: 10.3389/fphys.2026.1774714

OxLDL-induced ferroptosis and pyroptosis in atherosclerosis: a mini review (from Cardiology/Vascular Biology)
Shaozhi Liu; Yuxia Wu; Lei Chen; Liqin Hu; Jinjin Yin — Frontiers in Immunology 2026
Score: 5/10 | Pathways: NLRP3, VDAC1, urate-NLRP3, other

The paper's focus on NLRP3 inflammasome activation, GSDMD-mediated mitochondrial membrane targeting promoting lipid peroxidation, and bidirectional ferroptosis-pyroptosis crosstalk is tangentially relevant via the NLRP3/mitochondrial damage axis central to the SAMHD1 disease mechanism, but the oxLDL/atherosclerosis context and ferroptosis emphasis are not directly connected to SAMHD1 haploinsufficiency pathways.
DOI: 10.3389/fimmu.2026.1831457

Raccoon dog parvovirus NS1 protein antagonizes type I interferon signaling by promoting selective autophagic degradation of IRF3. (from Veterinary microbiology / virology)
Wenyu Cao; Rui-qi Wang; Jin-Yang Zheng; Ping Ma; Bo Hu — Veterinary microbiology 2026
Score: 5/10 | Pathways: cGAS-STING, ISG15-mitophagy, ME-CFS, other

This paper describes viral antagonism of the cGAS-STING-IRF3 axis via selective autophagic degradation of IRF3, directly implicating the same IRF3/IFN-β/ISG15 nodes central to the SAMHD1 interferonopathy mechanism, and the autophagic targeting of IRF3 offers an oblique parallel to the BECN1-ISGylation mitophagy block in the RED stream, but the context is a veterinary parvovirus with no direct relevance to SAMHD1 haploinsufficiency or human disease.
DOI: 10.1016/j.vetmic.2026.110934

PS4-05-23: Investigating Interferon Pathway Biomarkers as Predictors of Disease Free Survival in Triple Negative Breast Cancer (from Oncology (breast cancer / surgical pathology))
K. Yuan; S. Humble; A. Mabry; R. Kladney; L. Maggi — Clinical Cancer Research 2026
Score: 5/10 | Pathways: ISG15-mitophagy, JAK-STAT, BIK-cancer, other

ISG15 is a core effector in the RED pathway (ISGylation of MFN1/MFN2 and BECN1 causing mitophagy block), and this study directly investigates ISG15 expression as a prognostic biomarker in TNBC alongside ADAR1, providing clinical oncology context for ISG15's role in IFN-driven tumor-immune microenvironment modulation, though SAMHD1 and the specific haploinsufficiency mechanism are not addressed.
DOI: 10.1158/1557-3265.sabcs25-ps4-05-23

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Recent progress in cGAS-STING agonist design and mechanisms of cancer immune modulation. (from oncology/medicinal chemistry)
Wang Liao; Nafees Muhammad; Fei He; Hanif Muhammad; Yang Piaoping — 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target

This review covers cGAS-STING agonist design for cancer immunotherapy, touching the BLUE pathway's core signaling axis (cGAS→cGAMP→STING→IRF3→IFN-I), but focuses on activating rather than inhibiting this pathway and is oriented toward oncology rather than interferonopathy suppression, making it tangentially relevant at best—the therapeutic direction is opposite to what would benefit SAMHD1 haploinsufficiency patients.
DOI: 10.1039/d6cb00005c

Hyperglycaemia-induced metabolic stress and epigenetic imprinting in the inflammatory pathogenesis of diabetic neuropathy. (from Endocrinology/Neurology)
Faaz Bin Razi; Hamid Ashraf; S. Singhal; Ziaul Qamar; S. Moin — Diabetes research and clinical practice 2026
Score: 4/10 | Pathways: NLRP3, JAK-STAT, POLG-mtDNA, other

The paper discusses NLRP3 inflammasome activation, JAK/STAT signaling, and mitochondrial DNA as DAMPs in a hyperglycemia context, which are mechanistically relevant pathways in the SAMHD1 disease model, but the diabetic neuropathy framing and epigenetic focus are tangential to the core interferonopathy-mitochondrial syndrome without direct mechanistic overlap.
DOI: 10.1016/j.diabres.2026.113172

Antiaging Properties of the Klotho Protein (from Gerontology/nephrology)
G. J. Prud’homme; Qinghua Wang — Cells 2026
Score: 4/10 | Pathways: NLRP3, mTOR-lysosomal, other

Klotho's inhibition of NLRP3 inflammasome and NF-κB, mitochondrial ROS reduction, and autophagy modulation are tangentially relevant to the SAMHD1 interferonopathy-mitochondrial syndrome, but the paper does not address cGAS-STING, ISG15, VDAC1, or the dNTP pool mechanisms central to this disease, making the connection indirect background context only.
DOI: 10.3390/cells15060507

Mechanistic insights into atorvastatin-induced hepatotoxicity: molecular pathways, clinical relevance, and strategies for safer personalized therapy (from hepatology/pharmacology)
Mohammed A Abdel-Rasol; Wael M. El-Sayed — Clinical and Experimental Medicine 2026
Score: 4/10 | Pathways: NLRP3, VDAC1, mTOR-lysosomal, clinical-phenotype, other

The paper touches on NLRP3 inflammasome activation, mitochondrial dysfunction, and bile acid dysregulation in a hepatic context that is tangentially relevant to the family's hepatology phenotype (cholecystectomy clustering, hepatic steatosis) and the NLRP3/mitochondrial damage streams in the disease mechanism, but the focus is on drug-induced hepatotoxicity from atorvastatin rather than any intrinsic innate immune or SAMHD1-related pathway.
DOI: 10.1007/s10238-026-02091-w

Neutrophil extracellular traps in atherothrombosis (from Cardiology/vascular biology)
Ming Xue; Xin Li; Songhai Li; Jing Yang — Chinese Bulletin of Life Sciences 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, urate-NLRP3, other

The paper touches several core pathways (NLRP3 inflammasome, cGAS-STING via mtDNA release, mitochondrial dysfunction) as drivers of NETosis in atherosclerosis, which are mechanistically relevant to the SAMHD1 interferonopathy framework, but the primary subject is NETs in cardiovascular disease and there is no direct connection to SAMHD1, haploinsufficiency, or the specific family phenotype.
DOI: 10.3724/cbls.2026010

Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis. (from Nephrology)
Li Wen; Zhou Liang; Zhang Jinji; Sun Jingying; Feng Qing — 2026
Score: 3/10 | Pathways: NLRP3, mTOR-lysosomal, other

This review covers pyroptosis/NLRP3 and autophagy in renal fibrosis context, which are mechanistically relevant pathways in the disease model, but the organ focus (kidney fibrosis) and disease context (renal pathology) are not part of the family phenotype profile, making the connection largely tangential.
DOI: 10.1007/s10495-026-02358-3

ASS1 Promotes Atherosclerotic Inflammation Through the NLRP3/IL-33/ST2 Axis in Ox-LDL–Induced Foam Cells (from Cardiology/Vascular Biology)
Shaoyu Wu; Feihuang Han; Z. Qiao; S. Yuan; Xiaohui Bian — Frontiers in Bioscience-Landmark 2026
Score: 3/10 | Pathways: NLRP3, other

The paper examines NLRP3 inflammasome activation in foam cells via ASS1/STAT3/IL-33, which shares the NLRP3 node with the SAMHD1 disease mechanism, but the upstream driver (ox-LDL/argininosuccinate metabolism in atherosclerosis) is entirely distinct from the dGTP/urate/mtDNA-driven NLRP3 activation in SAMHD1 haploinsufficiency, with no mechanistic overlap in cGAS-STING, VDAC1, ISG15, or mitochondrial dNTP pathways.
DOI: 10.31083/fbl47686

Oxidative Stress and Inflammatory Pathways in Male Infertility: Molecular Mechanisms and Therapeutic Strategies (from andrology/reproductive medicine)
R. Zhankina; N. Tanideh; A. Botabayeva; U. Zhanbyrbekuly — West Kazakhstan Biomedicine Journal 2026
Score: 3/10 | Pathways: NLRP3, other

The paper discusses NLRP3 inflammasome activation and mitochondrial ROS in a reproductive context, which shares surface mechanistic overlap with the NLRP3 and mitochondrial dysfunction arms of the SAMHD1 pathomechanism, but the connection is entirely tangential — it does not address SAMHD1, cGAS-STING, interferonopathy, dNTP pool dysregulation, or any of the core molecular players, and male infertility is not a documented family phenotype.
DOI: 10.4103/wkbj.wkbj_17_26

Precision Neurodegeneration: Integrating Molecular Mechanisms, Biomarkers, and Targeted Therapeutics. (from Neurology/neurodegeneration)
Guizhen Lyu; Dongbing Li — CNS & neurological disorders drug targets 2026
Score: 3/10 | Pathways: NLRP3, ISG15-mitophagy, mTOR-lysosomal

While the paper mentions NLRP3 inflammasome and PINK1-Parkin mitophagy as therapeutic nodes in neurodegeneration, these are discussed in the generic context of Alzheimer's/Parkinson's disease without any mechanistic connection to SAMHD1, interferonopathy, cGAS-STING, or the dNTP pool dysregulation central to the disease profile.
DOI: 10.2174/0118715273435428251202075956

The IFIT3 Protein of Porcine Induces Interferon Signaling and Inhibits the Early Gene Expression of African Swine Fever Virus (from veterinary virology)
Wen-Li Wang; Deng-Wu Han; Xing Yang; Xijuan Shi; Yesheng Shen — Viruses 2026
Score: 3/10 | Pathways: JAK-STAT, ISG15-mitophagy, other

This paper characterizes porcine IFIT3 (ISG60) as an antiviral ISG acting through STAT1/TBK1/IRF3 and JAK-STAT signaling, touching on ISG15 and IRF3 which are nodes in the disease mechanism, but the work is focused on ASFV restriction in swine macrophages with no direct relevance to SAMHD1, human interferonopathy, mitochondrial dysfunction, or the family's clinical phenotypes.
DOI: 10.3390/v18050566

Abstract C043: Novel insights into the immunoregulatory role of radiation activated club cells in non-small cell lung cancer (from Radiation oncology / lung cancer immunology)
Aakanksha R Kapoor; Arshdeep Singh; Bharati Swami; Yongfeng He; Vivek Mittal — Cancer Immunology Research 2026
Score: 3/10 | Pathways: JAK-STAT, ISG15-mitophagy, other

While the paper documents radiation-induced Type I interferon/ISG15/STAT1 upregulation in lung club cells — pathways central to the SAMHD1 interferonopathy mechanism — the context is entirely radiation-oncology/NSCLC tumor microenvironment with no connection to SAMHD1, dNTPase biology, mitochondrial dysfunction, or the family's clinical phenotype.
DOI: 10.1158/2326-6074.io2026-c043

Pathway Coverage This Week

  • NLRP3: 32 papers
  • cGAS-STING: 30 papers
  • POLG-mtDNA: 29 papers
  • VDAC1: 23 papers
  • treatment-target: 23 papers
  • other: 23 papers
  • ISG15-mitophagy: 16 papers
  • mTOR-lysosomal: 12 papers
  • JAK-STAT: 9 papers
  • ME-CFS: 7 papers
  • clinical-phenotype: 5 papers
  • urate-NLRP3: 4 papers
  • BIK-cancer: 3 papers
  • dNTPase: 1 papers
  • AGS-spectrum: 1 papers
  • IRF7-metabolic: 1 papers

SAMHD1 Research Digest — 2026-05-24

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 6 papers evaluated | 4 high-relevance (≥7) | 2 medium (5–6) | 0 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Mitochondrial DNA-mediated cGAS-STING activation and its crosstalk with NLRP3 inflammasome in chronic obstructive pulmonary disease. (from Pulmonology/Respiratory Medicine)
Jindal Disha; Chopra Vishal; Garg Kranti; Sharma Siddharth — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, VDAC1, ME-CFS

This paper directly addresses the two core parallel inflammatory streams of the disease model—mtDNA-mediated cGAS-STING activation (BLUE pathway) and NLRP3 inflammasome crosstalk (PURPLE/GOLD pathways)—in a context of chronic oxidative mtDNA damage and cytosolic mtDNA release, mechanistically mirroring the SAMHD1 haploinsufficiency syndrome even though COPD is the disease context.
DOI: 10.1016/j.cytogfr.2026.05.001

Piezo1 mediates hypoxia-induced endometriosis fibrosis via the mtDNA -dependent cGAS-STING pathway. (from Gynecology/reproductive medicine)
Ouyang Zhuqing; Zhang Lanyue; Tan Jiarong; Shen Fujin — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, clinical-phenotype

This paper directly demonstrates the mtDNA leakage → cGAS-STING activation axis as a driver of fibrosis, a core Blue pathway mechanism in the SAMHD1 syndrome, and contextualizes it in a gynecological tissue relevant to the family's endometrial carcinoma phenotype, while the Ca²⁺-dependent mitochondrial damage mechanism provides a novel upstream trigger converging on the same cGAS-STING node.
DOI: 10.1186/s12967-026-08255-2

Mitochondrial DNA release contributes to neuropathic pain via a cGAS-STING-IRF3-CMPK2-associated immunometabolic feedback mechanism. (from Neurology/pain medicine)
Wang Bo; Zeng Hui; Zhan Hongrui; Xu Yin; Hu Ziwei — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, ME-CFS, other

This paper directly characterizes an IRF3-CMPK2 positive feedback loop downstream of mtDNA-cGAS-STING activation — where CMPK2 (a dNTP synthesis enzyme) sustains mitochondrial stress and mtDNA release — which maps precisely onto the BLUE stream (VDAC1→mtDNA escape→cGAS→STING→IRF3) of the SAMHD1 haploinsufficiency mechanism, and introduces CMPK2-mediated dNTP pool dysregulation as a novel amplification node that is highly relevant to the dNTPase-deficient context of SAMHD1 p.A565T; NDGA as a pharmacological inhibitor of this loop also represents a potential treatment target.
DOI: 10.1186/s12967-026-08314-8

Jintiange ameliorates age-related sarcopenia by inhibiting the cGAS-STING signaling pathway via maintaining mitochondrial homeostasis. (from Ethnopharmacology/Musculoskeletal medicine)
Xu Yuan; Li Xiao-Li; Guo Yi-Xun; Wu Ruo-Bing; He Ming-Chao — 2026
Score: 7/10 | Pathways: cGAS-STING, ISG15-mitophagy, POLG-mtDNA, treatment-target, other

This paper directly demonstrates that inhibiting cGAS-STING via mitochondrial homeostasis maintenance (PGC-1α biogenesis, MFN1 dynamics, PINK1/Parkin mitophagy) ameliorates sarcopenia, hitting three of the four core disease streams (BLUE cGAS-STING, RED ISGylation-mitophagy block, PURPLE mtDNA quality) simultaneously, and identifies a treatment modality acting upstream of the same nodes relevant to SAMHD1 haploinsufficiency pathology.
DOI: 10.1016/j.jep.2026.121873

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

A novel bifunctional peptide predicted to target neuropeptide Y4 and GLP-1 receptors alleviates cognitive deficits in 5 × FAD mice by modulating cGAS-STING-mediated neuroinflammation. (from Neurology/Alzheimer's disease pharmacology)
Feng Yijie; Zhang Caili; Wei Yinuo; Liu Enhua; Sun Hongyu — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, NLRP3, treatment-target, other

This paper directly demonstrates that cytosolic mtDNA release activates cGAS-STING-IRF3-IL-1β neuroinflammatory signaling (a core Loop A/B pathway in the SAMHD1 disease model) and that pharmacological suppression of this axis is therapeutically beneficial, providing mechanistic and treatment-relevant data for the mtDNA-cGAS-STING cascade central to SAMHD1 haploinsufficiency, albeit in an AD rather than interferonopathy context.
DOI: 10.1016/j.bcp.2026.118074

Fucoxanthin improves stomatitis by regulating mitochondrial function and cGAS-STING signaling. (from Dentistry/oral medicine)
Lin Caipeng; Deng Lili; Xie Xi; Luo Hai-Bin; Liu Deyu — 2026
Score: 5/10 | Pathways: cGAS-STING, POLG-mtDNA, treatment-target, other

This paper demonstrates that mitochondrial dysfunction leads to mtDNA release activating cGAS-STING (directly relevant to the BLUE stream of the disease mechanism), and identifies fucoxanthin as a direct cGAS/STING inhibitor with molecular docking evidence, but the context is stomatitis/oral mucositis rather than any of the core family phenotypes, making it an indirect therapeutic lead rather than mechanistically central.
DOI: 10.1038/s41598-026-53680-4

Pathway Coverage This Week

  • cGAS-STING: 6 papers
  • POLG-mtDNA: 6 papers
  • other: 4 papers
  • VDAC1: 3 papers
  • treatment-target: 3 papers
  • NLRP3: 2 papers
  • ME-CFS: 2 papers
  • clinical-phenotype: 1 papers
  • ISG15-mitophagy: 1 papers

SAMHD1 Research Digest — 2026-05-17

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 12 papers evaluated | 7 high-relevance (≥7) | 3 medium (5–6) | 2 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

NOX2 inhibitor baicalein alleviates rheumatoid arthritis and inactivating mitochondrial oxidative stress-mediated cGAS-STING signaling in fibroblast-like synoviocytes. (from Rheumatology)
Wang Rui; Fang Weiming; Qiao Yansheng; Zhang Xin; Gao Yuan — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, treatment-target, clinical-phenotype, other

This paper directly characterizes the NOX2→mtROS→VDAC1 oligomerization→mtDNA release→cGAS-STING axis in rheumatoid arthritis fibroblast-like synoviocytes, precisely mapping the BLUE-stream mechanism (VDAC1 macropore → cytosolic mtDNA → cGAS → STING → IFN-I) that is central to the SAMHD1 A565T interferonopathy model, while also identifying baicalein as a pharmacological intervention point and linking it to a clinically relevant autoimmune phenotype present in the family.
DOI: 10.1016/j.phymed.2026.158268

Macrophage TRPML1 ameliorates post-myocardial infarction inflammation by blocking VDAC1 oligomerization to prevent ferroptosis and cGAS-STING activation. (from Cardiology (post-myocardial infarction inflammation and cardiac repair))
Zhao Xiuye; Wang Jia; Wang Zhenru; Du Haonan; Li Hongda — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, NLRP3, POLG-mtDNA, treatment-target, mTOR-lysosomal

This paper directly demonstrates that VDAC1 oligomerization drives mtDNA cytosolic escape → cGAS-STING activation → pro-inflammatory cytokine storm in macrophages, and identifies VDAC1 inhibition (NSC 15364) as a therapeutic rescue strategy — mechanistically identical to the BLUE stream of the SAMHD1 A565T syndrome (SAMHD1/VDAC1 interaction loss → VDAC1 macropore → cytosolic mtDNA → cGAS → STING → IFN-I), making it highly relevant as both mechanistic validation and a potential treatment target.
DOI: 10.1016/j.freeradbiomed.2026.05.006

Tempol alleviates autoimmune uveitis by targeting the oxidative stress-mediated cGAS-STING-NF-kB signaling pathway to restore M1/M2 macrophage polarization balance. (from Ophthalmology/Autoimmune uveitis)
Xu Shuqin; Feng Jiaye; Peng Yuan; Xu Furu; Liu Yunfeng — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, treatment-target, other

This paper directly demonstrates the oxidative stress → mitochondrial damage → cytosolic mtDNA release → cGAS-STING-NF-κB → IFN-β → M1 macrophage polarization axis with impaired PINK1/Parkin mitophagy, which maps precisely onto the BLUE and RED streams of the SAMHD1 haploinsufficiency mechanism, and identifies Tempol (a superoxide dismutase mimetic/ROS scavenger) and STING inhibitor H-151 as therapeutic interventions that restore mitophagy flux and suppress interferon output—directly actionable for the family's convergent interferon-mitochondrial syndrome.
DOI: 10.1016/j.intimp.2026.116798

Mitochondrial dysfunction due to myeloid TFAM loss limits senolytic efficacy in allergic airway inflammation. (from Pulmonology/Allergy)
Nguyen Jackie; Van Courtney; Olverson Zianne A; Sampath Neil; Posham Lalithya — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, ISG15-mitophagy, other

This paper directly demonstrates that TFAM loss causes cytosolic mtDNA accumulation activating cGAS-STING signaling in macrophages, driving senescence-associated inflammation — a mechanistic parallel to the SAMHD1 BLUE pathway where VDAC1 macropore release of mtDNA fragments activates cGAS-STING-IRF3-IFN-I, and the finding that mitochondrial DNA maintenance failure amplifies innate immune activation is directly relevant to understanding how SAMHD1 haploinsufficiency sustains chronic interferonopathy via cytosolic mtDNA.
DOI: 10.1093/ajrcmb/aanag101

MSTO1 modulates RAD51 activity to safeguard mitochondrial DNA integrity and control immune responses. (from mitochondrial biology / rare neuromuscular disease)
Cheng Kaiqi; Xu Zhanzhan; Liu Jiansong; Pan Yichen; Nie Chen — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, ME-CFS, other

MSTO1 deficiency causes RAD51-mediated mtDNA damage, BAX/BAK-dependent mtDNA leakage activating cGAS-STING inflammation—directly paralleling the BLUE stream (VDAC1 macropore → cytosolic mtDNA → cGAS → IFN-I) and POLG-mtDNA integrity mechanisms central to the SAMHD1 A565T interferonopathy model, offering a novel upstream regulator of the same mtDNA-immune axis.
DOI: 10.1038/s41417-026-01032-9

α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron-microglia communication. (from Neuroscience/neurodegeneration)
Chakraborty Ranabir; Maya Stephanie; Testa Veronica; Montero-Muñoz Jara; Nonaka * — 2026
Score: 7/10* | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, mTOR-lysosomal, other

This paper directly demonstrates the mechanistic chain of mitochondrial damage → cytosolic mtDNA release → cGAS-STING-IRF3 activation that constitutes Loop A/B of the SAMHD1 haploinsufficiency model, and further shows that damaged mitochondria are transferred intercellularly and degraded via lysosomal pathways, with NF-κB and IRF3 driving inflammatory amplification—all core molecular players in the disease mechanism, albeit in a synucleinopathy context rather than SAMHD1-specific.
DOI: 10.1038/s41467-026-73136-7

Mechano-metabolic feedback connects tissue fluidity to mitochondrial DNA-dependent immunity in breast cancer. (from Oncology / tumor mechanobiology)
Palamidessi Andrea; Frittoli Emanuela; Corada Monica; Martini Emanuele; Barzaghi — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, BIK-cancer, other

This paper directly demonstrates a mtDNA-release → cGAS-STING → innate immune hyperinflammation axis in cancer, mediated by BAX/BAK outer mitochondrial membrane permeabilization and GASDERMIN A oligomerization, which is mechanistically analogous to the SAMHD1/VDAC1 macropore → cytosolic mtDNA → cGAS-STING loop (Loop A/B) in the disease model, and provides novel upstream (mechano-metabolic, mitochondrial fission via AMPK-AKAP1-DRP1) and downstream (tumor immunogenicity, checkpoint sensitivity) context relevant to SAMHD1 haploinsufficiency-driven interferonopathy and cancer susceptibility.
DOI: 10.1038/s41467-026-71795-0

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

cGAS-STING Signalling in the tumour microenvironment: Implications for immune surveillance and therapeutic strategies. (from Oncology / tumour immunology)
Al-Adayleh Teeb Yasir Mahmoud; Ahmad Waqas; Rahiman Siti Sarah Fazalul; Murugaiy — 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, POLG-mtDNA, mTOR-lysosomal, treatment-target, other

This review covers the cGAS-STING pathway in depth—including mtDNA release as a trigger, STING-NF-κB crosstalk, autophagy interactions, and pharmacological modulators—all directly relevant to the BLUE stream of the SAMHD1 interferonopathy mechanism, but is framed entirely around oncology/TME rather than monogenic interferonopathy or SAMHD1 haploinsufficiency.
DOI: 10.1016/j.intimp.2026.116832

O-GlcNAcylation of p66Shc drives senescence associated secretory phenotype via mitochondrial DNA release in gestational diabetes mellitus†. (from Obstetrics/reproductive medicine)
Zhu Hengxuan; Ji Lulu; Lai Rujie; Nai Yaru; Yang Xiting — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, pregnancy-fetal, other

This paper directly demonstrates cytoplasmic mtDNA release activating cGAS/STING to drive senescence-associated secretory phenotype and inflammation in a gestational/placental context, which is mechanistically adjacent to the BLUE stream (VDAC1→mtDNA→cGAS→STING→IFN-I) and relevant to the pregnancy-fetal phenotype dimension of the family profile, though the driver is p66Shc O-GlcNAcylation under high glucose rather than SAMHD1 haploinsufficiency.
DOI: 10.1093/biolre/ioag090

Recent advances in dual-function fluorescent ligands targeting mitochondrial DNA G-Quadruplexes for Cancer Theranostics. (from oncology/chemical biology)
Hu Ming-Hao — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, NLRP3, VDAC1, treatment-target, other

This review is adjacently relevant because mtG4-targeting ligands directly perturb mitochondrial DNA integrity and dNTP pool dynamics (core to SAMHD1 haploinsufficiency pathology), activate cGAS-STING via cytosolic mtDNA release, and trigger NLRP3-associated PANoptosis—all three major mechanistic streams (BLUE, PURPLE, GOLD) of the SAMHD1 interferonopathy model—while the cancer theranostics framing connects to the family's oncological phenotypes (prostate, myeloma, endometrial cancers) and offers potential treatment-target insights via mitochondrial metabolic collapse strategies.
DOI: 10.1016/j.bmc.2026.118697

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

A prognostic model based on nucleotide metabolism genes in osteosarcoma. (from oncology)
Ju Songli; Tao Lu; Li Xuyan; Huang Nijiao; Ke Xixian — 2026
Score: 4/10 | Pathways: dNTPase, BIK-cancer, IRF7-metabolic, other

SAMHD1 is included as one of seven nucleotide metabolism genes in an osteosarcoma prognostic model, confirming its role in metabolic reprogramming and tumor suppression, but the paper does not investigate SAMHD1 mechanism, haploinsufficiency, dNTPase activity, or any of the core interferon-mitochondrial pathways relevant to this disease profile.
DOI: 10.1007/s12672-026-05036-7

A cell-impermeable kinase inhibitor uncovers outside-in signaling pathways that promote HIV-1 infection. (from Virology/HIV research)
Vinzant Kelsey; Cheshenko Natalia; Pan Heng; Cutler Ronald; Buckler Joshua N — 2026
Score: 4/10 | Pathways: dNTPase, other

The paper touches on SAMHD1 only as a CDK-phosphorylation target (phospho-SAMHD1 inactivating its dNTPase activity to promote HIV infection), which is tangentially related to the core disease mechanism of reduced SAMHD1 dNTPase activity, but the study is focused on HIV entry/infection mechanisms and exofacial signaling rather than interferonopathy, mitochondrial dysfunction, or any pathway directly relevant to the A565T haploinsufficiency syndrome.
DOI: 10.1128/jvi.00160-26

Pathway Coverage This Week

  • other: 11 papers
  • cGAS-STING: 10 papers
  • VDAC1: 8 papers
  • POLG-mtDNA: 8 papers
  • treatment-target: 5 papers
  • mTOR-lysosomal: 3 papers
  • NLRP3: 2 papers
  • ISG15-mitophagy: 2 papers
  • BIK-cancer: 2 papers
  • dNTPase: 2 papers
  • clinical-phenotype: 1 papers
  • ME-CFS: 1 papers
  • JAK-STAT: 1 papers
  • pregnancy-fetal: 1 papers
  • IRF7-metabolic: 1 papers

SAMHD1 Research Digest — 2026-05-10

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 37 papers evaluated | 12 high-relevance (≥7) | 20 medium (5–6) | 5 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

Mitochondrial 8-Oxoguanine DNA Glycosylase 1–Mitochondrial Permeability Transition Pore Axis Drives Mitochondrial DNA Escape and Accelerates Osteoarthritis Progression (from Orthopedics/osteoarthritis)
Shiqian Huang; Heting Yu; Weizhong Qi; Na Lin; Jianmao Chen — Research 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, NLRP3, treatment-target, other

This paper directly demonstrates the OGG1-mPTP axis driving oxidized mtDNA escape → cytosolic mtDNA → cGAS-STING-NF-κB activation, mechanistically recapitulating the BLUE and PURPLE streams of the SAMHD1 A565T syndrome (VDAC1/mPTP-mediated mtDNA release and ox-mtDNA from impaired mitochondrial repair both feeding cGAS-STING), while cyclosporin A (mPTP inhibitor) and TH10785 (OGG1 activator) as intervention targets are directly translatable to therapeutic strategies for the dNTP pool expansion–driven mitochondrial pathology in SAMHD1 haploinsufficiency.
DOI: 10.34133/research.1235

Crosstalk between cGAS-STING and pyroptosis: From molecular mechanisms to therapeutic strategies. (from Pharmacology/drug discovery)
Hongquan Wang; Shuang Wu; Xuan Zhang; WeiHua Zheng; Zhiji Wang — International immunopharmacology 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, VDAC1, treatment-target, AGS-spectrum, ME-CFS

This review directly addresses the cGAS-STING–pyroptosis (NLRP3/caspase-1) crosstalk that constitutes Loops A and B of the SAMHD1 haploinsufficiency mechanism, covers therapeutic targeting strategies including upstream nucleic acid sensing, core pathway modulation, and downstream effector control that map precisely onto proposed interventions (IMSB301, MCC950, VBIT-4), and frames these in autoimmune/interferonopathy and sterile inflammation contexts highly relevant to the family's convergent interferon-mitochondrial syndrome.
DOI: 10.1016/j.intimp.2026.116203

Emerging molecular mechanisms of cGAS-STING activation and regulation. (from Structural/molecular biology)
Yilin Liu; Kanglong Ma; Zhengfan Jiang — Molecular immunology 2026
Score: 8/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, ME-CFS, treatment-target

This review directly covers the cGAS-STING pathway (Loop A in the disease mechanism), including structural activation by dsDNA, cGAMP synthesis and STING translocation, and novel regulatory mechanisms (sGAGs, biocondensates, manganese-independent activation) that are directly relevant to understanding how VDAC1 macropore-released cytosolic mtDNA fragments drive IRF3→IFN-I signaling in SAMHD1 haploinsufficiency, and identifies therapeutic targets applicable to this interferonopathy.
DOI: 10.1016/j.molimm.2026.02.008

The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor (from oncology)
Kui Zhao; Siyuan Cui; Na Wang; Qi Wei; Xuerui Wang — Journal of Translational Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, JAK-STAT, mTOR-lysosomal, treatment-target, IRF7-metabolic

This review directly addresses the cGAS-STING/mitochondrial metabolism axis—the BLUE stream of the disease mechanism—including mtDNA escape, STING spatiotemporal dynamics, and metabolic crosstalk that mirrors the interferonopathy-mitochondrial loop in SAMHD1 haploinsufficiency, while the treatment-target discussion of STING agonist optimization and metabolic modulation has translational relevance for the family's interferonopathy management.
DOI: 10.1186/s12967-026-07748-4

Mitochondrial DNA 6mA Methylation by METTL4 Drives Neuroinflammation via cGAS-STING Activation in Vascular Cognitive Impairment. (from Neurology/cerebrovascular)
Z. Gong; Ziyi Chen; Shuixian Sang; Lingfei Yang; H. Qin — Free radical biology & medicine 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, other

This paper directly demonstrates the mechanistic axis of oxidized mtDNA leakage activating cGAS-STING neuroinflammation—a core BLUE stream pathway in the SAMHD1 haploinsufficiency model—and introduces METTL4-mediated mtDNA epigenetic modification as an upstream driver of mtDNA escape, impaired ETC activity, and ROS production that converges on the same cGAS-STING-mediated inflammatory cascade relevant to the proband's interferon-mitochondrial syndrome.
DOI: 10.1016/j.freeradbiomed.2026.01.019

The roles of the mtDNA-cGAS-STING axis in tumor immunity: from immune activation to immune evasion (from Oncology/tumor immunology)
Na Huang; Zheng Liu; Haibo Lei; Xiang Liu — Frontiers in Immunology 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, JAK-STAT, IRF7-metabolic, BIK-cancer, treatment-target

This review directly covers the mtDNA-cGAS-STING-IRF3-IFN-I axis (the BLUE stream of the disease mechanism) in comprehensive detail, including mtDNA leakage triggers, cGAMP synthesis, downstream IFN-I induction, and therapeutic targeting strategies (STING modulators, nano-delivery), all of which are core to SAMHD1 haploinsufficiency pathophysiology, though the tumor immunity framing is tangential to the primary interferonopathy/ME-CFS phenotype.
DOI: 10.3389/fimmu.2025.1739559

mtDNA leakage promotes neuron-glia crosstalk to induce epilepsy by cGAS-STING-driven neuroinflammation and serine metabolic reprogramming. (from Neurology/Epileptology)
Jie Jiang; Meiling Zuo; Kehan Zhao; Zhihao Ling; Zhida Wu — Proceedings of the National Academy of Sciences of the United States of America 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, NLRP3, treatment-target, other

This paper directly demonstrates the mtDNA leakage → cGAS-STING → neuroinflammation axis in a CNS context, with pharmacologic STING inhibition (H-151) suppressing disease, providing mechanistic and therapeutic validation for the BLUE stream of the SAMHD1 haploinsufficiency model, while also introducing a novel metabolic reprogramming downstream consequence (D-serine/NMDA excitotoxicity) that could explain neurological phenotypes (ASD/ADHD, possible seizure susceptibility) in the family.
DOI: 10.1073/pnas.2522313123

Protective and pathogenic: The Janus-faced role of cGAS-STING in the brain. (from Neurology/cerebrovascular)
C. Corona; Christina Kanzlemar; A. Hussaini; R. Ratan — Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2026
Score: 7/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, ME-CFS, AGS-spectrum, mTOR-lysosomal

This paper directly characterizes cGAS-STING/IFN-I signaling as enforcing a 'metabolic austerity program' that suppresses synaptic plasticity when chronically activated—a mechanism highly relevant to the SAMHD1 A565T family's neurocognitive phenotypes (AuDHD, cognitive fatigue, ME/CFS) driven by constitutive BLUE-stream cGAS-STING activation, and the distinction between transient vs. sustained IFN-I activation maps directly onto the haploinsufficiency's tonic low-grade interferonopathy.
DOI: 10.1177/0271678X261427904

CircZBTB44-Encoded Peptide ZBTB44-342aa Alleviates Aortic Valve Calcification Via cGAS-STING Inhibition. (from Cardiology / valvular disease)
Dongtu Hu; Yingwen Lin; Hai-Bo Huang; G. Xian; Yubing Chen — Circulation research 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target

This paper directly demonstrates that mtDNA cytosolic release activates cGAS-STING to drive pathological osteogenic differentiation, and identifies STING inhibition (H-151) as therapeutic—mechanistically parallel to the BLUE stream (VDAC1 → mtDNA escape → cGAS → STING → IRF3 → IFN-I) central to the SAMHD1 A565T syndrome, with the added novel mechanistic detail that IGF2BP3 suppresses mitochondrial damage and mtDNA release upstream of cGAS-STING.
DOI: 10.1161/CIRCRESAHA.125.326771

Targeting the cGAS-STING-TBK1 pathway in cancer therapy. (from Oncology)
Leyao Jiang; Y. Zhong; Zilong Zhang; Qicheng Yang; Shengting Sun — Future medicinal chemistry 2026
Score: 7/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, treatment-target, BIK-cancer

This review directly covers the cGAS-STING-TBK1 axis—the BLUE stream core pathway in the disease mechanism—including its dual role in cancer (relevant to SAMHD1 tumor suppressor function) and targeted therapeutic agents such as STING agonists/antagonists and TBK1 inhibitors that represent treatment candidates for the interferonopathy component of the syndrome.
DOI: 10.1080/17568919.2026.2628553

Abstract 389: GSDMB drives cGAS-STING-mediated immune evasion in HER2-amplified colorectal cancer. (from Oncology (colorectal cancer / HER2-amplified CRC))
Junyong Weng; Tianchen Xiong; Xinxiang Li; Ajay Goel — Cancer Research 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, JAK-STAT, BIK-cancer, other

GSDMB-driven mitochondrial membrane pore formation causing chronic low-level mtDNA leakage into the cytosol activating cGAS-STING with downstream IFNα response directly mirrors the BLUE pathway (VDAC1 macropore → cytosolic mtDNA → cGAS → STING → IRF3 → IFN-I) central to SAMHD1 haploinsufficiency, and demonstrates a novel pore-forming mechanism linking mitochondrial integrity loss to chronic interferonopathy in a cancer context relevant to the family's BIK-cancer axis.
DOI: 10.1158/1538-7445.am2026-389

Integrative transcriptomic profiling links telomere dysfunction to cGAS–STING activation in heart failure signatures in mice and humans (from Cardiology)
M. Brandt; S. Khraisat; Q. Luo; M. Mayerle; U. Raaz — Cardiovascular Research 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, JAK-STAT, ISG15-mitophagy, clinical-phenotype

This paper provides first direct evidence that telomere shortening activates cGAS-STING → type I interferon signaling in cardiomyocytes via a telomere-p53-mitochondria axis, directly paralleling the BLUE and RED streams of the SAMHD1 haploinsufficiency mechanism (cytosolic DNA → cGAS → STING → IRF3 → IFN-I → JAK-STAT), and contextualizes interferon-driven cardiac dysfunction as a clinically relevant endpoint relevant to the family's interferonopathy cardiovascular risk.
DOI: 10.1093/cvr/cvag013

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

Simultaneous activation of apoptosis and cGAS-STING pathway with a mitochondria-targeted dehydrocholic acid compound for enhanced hepatocellular carcinoma chemoimmunotherapy. (from Oncology/pharmacology)
Fuwei Li; Sizhe Zhu; Xinyu Sun; Guangxing Geng; Jiawen Zhao — Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, BIK-cancer, treatment-target

This paper directly demonstrates the mechanistic link between mitochondrial permeability transition pore opening, cytosolic mtDNA release, and cGAS-STING activation in hepatocellular carcinoma — recapitulating the BLUE stream of the SAMHD1 haploinsufficiency mechanism (VDAC1 macropore → cytosolic mtDNA → cGAS → STING → IRF3 → IFN-I) and is further relevant given the family's hepatic phenotype (hepatic steatosis, cholecystectomy clustering) and SAMHD1's tumor suppressor role, though the context is therapeutic oncology rather than constitutive interferonopathy.
DOI: 10.1016/j.biopha.2026.119044

Spleen Tyrosine Kinase (SYK) is Necessary for cGAS‐STING Signaling in Müller Glia and Visual Function Deficits in Diabetic Mice (from Ophthalmology/Retinal Neuroscience)
Esma I. Yerlikaya; S. Sunilkumar; Sandeep M. Subrahmanian; Allyson L. Toro; Clay — Glia 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, NLRP3, JAK-STAT, other

This paper directly demonstrates the mechanistic link between mitochondrial membrane permeability → cytosolic mtDNA → cGAS-STING → NF-κB → IL-1β/CCL2 (MCP-1) activation, which maps precisely onto the BLUE stream of the SAMHD1 haploinsufficiency model, and introduces SYK as a novel required intermediary in cGAS-STING signaling with potential therapeutic targeting relevance, though the disease context is diabetic retinopathy rather than SAMHD1 dysfunction.
DOI: 10.1002/glia.70155

Pharmacological activation of cGAS-STING pathway to reverse cancer drug resistance. (from oncology)
Yumin Wang; Yan Wang; Q. Gao; Yonglin Zhu; Yulin Li — Pharmacology & therapeutics 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, treatment-target, BIK-cancer, other

This review directly covers the cGAS-STING pathway—a core Loop A mechanism in SAMHD1 haploinsufficiency—and describes how epigenetic, post-translational, and metabolic suppression of cGAS-STING promotes drug resistance, which is directly relevant to understanding modulators of this pathway and potential therapeutic targets, though the oncology framing (reactivating a suppressed pathway) is the mirror-image of the disease context here (a constitutively hyperactive cGAS-STING from SAMHD1 loss-of-function), making it an adjacent rather than direct mechanistic match.
DOI: 10.1016/j.pharmthera.2026.108991

Mangiferin inhibits cGAS-STING pathway-related inflammation via Nrf2 activation to protect against sepsis-induced heart injury (from Cardiology/Traditional Chinese Medicine)
Junna Song; Meng Wang; Qian Li; Wanting Zhao; Xiangming Chen — Chinese Medicine 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other

This paper directly addresses mtDNA release, mitochondrial membrane integrity (mPTP/VDAC-adjacent), and cGAS-STING-driven cardiac inflammation with a natural compound (mangiferin/Nrf2) that suppresses the same cGAS-STING axis central to the SAMHD1 interferonopathy mechanism, offering a potentially translatable treatment angle for the interferon-mitochondrial syndrome, though the context is LPS-sepsis rather than SAMHD1 haploinsufficiency.
DOI: 10.1186/s13020-026-01329-9

Selenium regulates pyroptosis through the ROS-mtDNA-cGAS-STING axis to alleviate trimethyltin chloride-induced inflammation in chicken kidneys. (from Veterinary toxicology / comparative physiology)
Huiling Zheng; Xinyu Huo; Wenwen Zhang; Shuang Lou; Mingyue Li — Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, other

This paper directly demonstrates the ROS→mitochondrial dysfunction→mtDNA leakage→cGAS-STING→NLRP3/pyroptosis cascade (BLUE and PURPLE streams) and validates selenium as a therapeutic modulator of this axis, providing mechanistic and pharmacological context highly relevant to the SAMHD1 interferonopathy model where the same mtDNA-cGAS-STING-NLRP3 convergence is central, though the disease context (organotin nephrotoxicity in chickens) is entirely distinct from SAMHD1 haploinsufficiency.
DOI: 10.1016/j.cbpc.2026.110452

The Role of the cGAS-STING Pathway in Central Nervous System Diseases (from Neurology)
Xiangning He; Xunlu Yin; Qian Chen; Haoyuan Gao; Fangfang Zhao — CNS & Neurological Disorders - Drug Targets 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, treatment-target, ME-CFS

This review directly covers the cGAS-STING pathway (BLUE stream) in CNS disease contexts including neuroinflammation, autophagy, and apoptosis, with therapeutic inhibitors discussed (C-176, H-151, RU.521), which are directly relevant to the SAMHD1/VDAC1/cGAS/STING axis driving neurological manifestations (AuDHD, ME/CFS, potential dystonia) in this family, though it lacks SAMHD1-specific or mitochondrial dNTP-pool mechanistic content.
DOI: 10.2174/0118715273428657260309045542

Lipids Meet Immunity: Metabolic Control of cGAS-STING (from Lipidology/Immunometabolism)
C. Mah; Xuan Yuan Aw; Ngee Kiat Chua — Lipidology 2026
Score: 6/10 | Pathways: cGAS-STING, IRF7-metabolic, mTOR-lysosomal, other

This review directly addresses metabolic regulation of the cGAS-STING pathway—the BLUE stream core mechanism—through lipid biology, covering how lipid metabolism (including membrane compartmentalization, cholesterol, fatty acids) modulates STING activation and signaling dynamics, which is directly relevant to the VDAC1-mtDNA-cGAS-STING axis in this disease and adjacent to the hepatic steatosis and metabolic reprogramming phenotypes observed in the family.
DOI: 10.3390/lipidology3010010

The roles of cGAS-STING pathway in cancer (from Oncology)
Jijun Sun; Ruijuan Wang; Jue Wang; Lele Zhang — Oncology and Translational Medicine 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, IRF7-metabolic, BIK-cancer, treatment-target, clinical-phenotype

This review directly covers the cGAS-STING pathway (BLUE stream core mechanism) with extensions into pyroptosis/NLRP3 crosstalk and cancer contexts relevant to the family's tumor phenotypes (multiple myeloma, endometrial, prostate, duodenal cancers), and discusses STING agonists/inhibitors as therapeutic targets, but does not address SAMHD1, mitochondrial mechanisms, ISG15-mitophagy, or VDAC1 specifically.
DOI: 10.1097/ot9.0000000000000136

Resveratrol Mitigates Age-Associated Cognitive Decline via Inhibition of cGAS-STING-Mediated Microglial Senescence (from Neuroscience/gerontology)
Xinxin Duan; Jiahui Cheng; Jiayao Wang; Wen Chen; Zhi Ruan — Cells 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, ME-CFS, treatment-target

This paper directly investigates cGAS-STING pathway suppression as a therapeutic target for neuroinflammation and cognitive decline, with downstream IL-1β and CXCL-10 reduction highly relevant to the BLUE and RED streams of the SAMHD1 interferonopathy mechanism, and resveratrol's mechanism (potentially via SIRT1/PGC-1α activation and cGAS inhibition) offers a plausible treatment-target insight for managing chronic IFN-I signaling in SAMHD1 haploinsufficiency, though the context is aging/galactose-induced senescence rather than SAMHD1 mutation.
DOI: 10.3390/cells15060523

TRIM69 potentiates the cGAS-STING signalling pathway by promoting STING ubiquitination. (from Virology/antiviral innate immunity)
Shixin Chen; Li Yi; Mengzhou Xue; Chunfu Zheng — Cellular signalling 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, treatment-target

TRIM69-mediated K63-ubiquitination of STING enhances cGAS-STING-IFN-I signaling, directly relevant to the BLUE stream where SAMHD1/VDAC1 loss drives cytosolic mtDNA→cGAS→STING→IRF3→IFN-I, as a novel positive regulator that could amplify the already dysregulated interferonopathy in this family; however, no direct SAMHD1, mitochondrial, or clinical phenotype connection is demonstrated.
DOI: 10.1016/j.cellsig.2026.112495

cGAS-STING signaling: a therapeutic target in inflammatory bowel disease and related colorectal cancer (from Gastroenterology/Oncology)
Xi Chen; Xiaohua Tang; Sixuan Chen; Yang Ye; Fei Mao — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, NLRP3, treatment-target, IRF7-metabolic, clinical-phenotype

This review directly covers the cGAS-STING pathway (a core BLUE stream component in the disease mechanism) and its bidirectional regulation including IFN-I and proinflammatory cytokine production, with therapeutic targeting implications relevant to interferonopathy management, though it focuses on intestinal disease contexts rather than SAMHD1 haploinsufficiency or mitochondrial pathology specifically.
DOI: 10.3389/fimmu.2025.1709908

Targeting the cGAS-STING pathway in ophthalmology: from innate immunity to therapeutic innovation. (from Ophthalmology)
Dan Yan; Weijie Ouyang; Kuanshu Li; Xuguang Sun — Experimental eye research 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, mTOR-lysosomal, AGS-spectrum, treatment-target, clinical-phenotype

This review directly covers the cGAS-STING pathway (BLUE stream core mechanism) with therapeutic targeting implications, and notably flags glaucoma as a cGAS-STING-driven ocular disease—glaucoma appears in the tracked family phenotype list—providing a mechanistic bridge between the interferonopathy and a documented familial clinical feature, while the autophagy/senescence/cell-death interactions also touch ISG15-mitophagy and mTOR-lysosomal axes.
DOI: 10.1016/j.exer.2026.110978

Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications (from Oncology/Cancer Immunotherapy)
Lusheng Wang; Sudi Zhu; Zhixian Ding; Jie Hong; Lijie Zheng — Journal of Translational Medicine 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, treatment-target

This paper covers cGAS-STING signaling comprehensively in the tumor immunotherapy context, including cell-type-specific activation dynamics, chronic vs. acute signaling consequences, and therapeutic modulation strategies that are mechanistically relevant to the SAMHD1 haploinsufficiency disease model (where dysregulated cGAS-STING via VDAC1 macropore/mtDNA escape drives Loop A), but the focus is entirely oncologic/immunotherapeutic rather than interferonopathy or SAMHD1-related disease.
DOI: 10.1186/s12967-025-07645-2

Cutaneous human papillomavirus E6 impairs the cGAS-STING pathway (from Virology/Dermatology-oncology)
Grant Brooke; D. Dacus; Rose Pollina; Katsura Asano; N. Wallace — mSphere 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, other

This paper directly characterizes cGAS-STING pathway suppression by a viral protein (β-HPV E6), which is mechanistically relevant to the BLUE stream of the disease model where cytosolic dsDNA activates cGAS→STING→IRF3→IFN-I, but the context is viral immune evasion in skin cancer rather than SAMHD1 haploinsufficiency, making it an indirect connection that illuminates cGAS-STING modulation without direct mechanistic import to the family phenotype.
DOI: 10.1128/msphere.00859-25

Calibrating the RT-cGAS-STING axis to drive cold-to-hot tumor transformation: mechanistic foundations and translational strategies for combination with immunotherapy (from Radiation oncology / tumor immunology)
Yi-fan Kang; Jin-ming Chen; Bai Xu; Jun-Nv Xu; Qixian Qin — Molecular Cancer 2026
Score: 5/10 | Pathways: cGAS-STING, IRF7-metabolic, JAK-STAT, treatment-target, other

This review covers the cGAS-STING-IFN-I axis in depth (Loop A of the disease mechanism) and discusses regulatory nodes like TREX1 and apoptotic caspases, with translational treatment implications, but is framed entirely within radiotherapy-oncology and does not address SAMHD1, mitochondrial dNTP pools, VDAC1, ISG15-mitophagy, or the interferonopathy-fatigue spectrum relevant to this family.
DOI: 10.1186/s12943-026-02636-3

cGAS-STING Signaling Pathway in Urogenital Oncology: Regulation, Resistance, and Routes to Response. (from Oncology/Urology)
Chen Gong; Senmao Li; Ying Huang; Enxiu Luo; Zhiyong Tan — Critical reviews in oncology/hematology 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, BIK-cancer, treatment-target

This review covers cGAS-STING signaling in urogenital oncology with mechanistic detail on phosphorylation/ubiquitination regulation, STING agonists, and interferon competence circuits that are directly relevant to the BLUE stream of the SAMHD1 mechanism, and touches on prostate cancer (BIK-axis family phenotype), but remains oncology-focused and does not address SAMHD1, mitochondrial dysfunction, ISG15-mitophagy, or the interferonopathy/ME-CFS clinical context.
DOI: 10.1016/j.critrevonc.2026.105222

Loss of XRCC1 promotes cGAS/STING mediated innate immune signaling in gastric cancer (from Oncology/gastroenterology)
Aashirwad Shahi; Shengyuan Zhao; Julia A. Goewey Ruiz; Dawit Kidane — Molecular Medicine 2026
Score: 5/10 | Pathways: cGAS-STING, other

This paper mechanistically demonstrates that nuclear DNA repair deficiency (XRCC1 loss) triggers cytosolic DNA accumulation and cGAS/STING-mediated type I interferon signaling, which is directly analogous to the BLUE stream in the SAMHD1 A565T model where dNTP pool imbalance and VDAC1 dysfunction release mtDNA to activate cGAS/STING, but the specific molecular actors (XRCC1 vs. SAMHD1, nuclear SSBs vs. cytosolic dNTP/mtDNA) and clinical context (gastric cancer vs. interferonopathy) are sufficiently distinct to limit direct translational relevance.
DOI: 10.1186/s10020-026-01429-0

Abstract A003: Chronic cGAS–STING activation reprograms glioblastoma-associated macrophages toward immunosuppression in hypoxic tumor niches (from Neuro-oncology)
Sebastian Ouyang; Virginia Wertman; Michael Brown; Matthew S. Waitkus; Justin T. — Cancer Research 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, other

This paper directly investigates cGAS-STING signaling and demonstrates that chronic/sustained STING activation leads to loss of interferon signaling and metabolic reprogramming, which is mechanistically relevant to understanding how the constitutive low-level cGAS-STING activation hypothesized in SAMHD1 haploinsufficiency might paradoxically shift toward immunosuppression over time, but the context is glioblastoma tumor immunology rather than interferonopathy or mitochondrial disease.
DOI: 10.1158/1538-7445.brain26-a003

Venezuelan Equine Encephalitis Virus Antagonizes the cGAS-STING Pathway (from Virology/Infectious Disease)
Brittany N. Heath; Maryna Akhrymuk; Abdullahi Temitope Jamiu; I. Akhrymuk; A. Pi — Cells 2026
Score: 5/10 | Pathways: cGAS-STING, ISG15-mitophagy, JAK-STAT, ME-CFS, other

This paper directly investigates cGAS-STING pathway modulation by an RNA virus (VEEV), demonstrating viral antagonism of STING phosphorylation and noncanonical ISG induction, which is mechanistically relevant to the BLUE and RED streams of the SAMHD1 syndrome (where dysregulated cGAS-STING drives IFN-I → ISGylation → mitophagy block), and the post-viral ME/CFS trigger context (adenovirus/SARS-CoV-2 in proband), but the connection is indirect as VEEV is not a documented trigger and no SAMHD1 or haploinsufficiency data are presented.
DOI: 10.3390/cells15040327

Pueraria flavones attenuate DSS-induced colitis by regulating the microbiota-bile acid-FXR/TGR5 axis and suppressing mtDNA-cGAS-STING signaling (from Gastroenterology/Pharmacognosy)
Liheng Kang; Chunsheng Feng; Ziyi Tang; Wanping Gu; Ying Wang — iScience 2026
Score: 5/10 | Pathways: cGAS-STING, POLG-mtDNA, other

This paper directly demonstrates the mtDNA-release → cGAS-STING axis as a colitis driver and its suppression by a therapeutic agent, which is mechanistically relevant to the BLUE stream (VDAC1/mtDNA/cGAS/STING/IFN-I) of the SAMHD1 syndrome, but the colitis context, plant flavone intervention, microbiota-bile acid framing, and absence of any interferonopathy/SAMHD1 connection make it only an indirect mechanistic parallel rather than a directly actionable finding.
DOI: 10.1016/j.isci.2026.115275

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer (from Oncology/Radiation Oncology)
Trang Thao Quoc Pham; Pei-Ju Lee; Nguyen Quoc Khanh Le — iScience 2026
Score: 4/10 | Pathways: cGAS-STING, other

The paper discusses cGAS/STING in the context of colorectal cancer radiosensitivity and complement C5a/C5aR1 suppression of STING-driven IFN-beta, which touches the cGAS-STING pathway central to the BLUE stream, but the oncologic and radiotherapy framing is tangential to the SAMHD1 haploinsufficiency interferonopathy mechanism and adds no direct mechanistic or clinical insight relevant to the family phenotype.
DOI: 10.1016/j.isci.2026.115009

Targeting redox metabolism and low-dose radiotherapy synergistically activate cGAS-STING pathway to improve NK cell therapy efficacy in hepatocellular carcinoma (from Oncology/Nanomedicine)
Bo Liu; Wenjia Kong; Xijie Zhang; Bo Ren; Yusheng Cheng — Journal of Nanobiotechnology 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target, other

This paper involves cGAS-STING pathway activation as a mechanism but in the context of HCC tumor immunotherapy via redox manipulation and NK cell recruitment, with no connection to SAMHD1 haploinsufficiency, interferonopathy, mitochondrial dNTP pools, or any family phenotype; the cGAS-STING relevance is mechanistically superficial relative to the disease profile.
DOI: 10.1186/s12951-026-04171-1

EEPD1 Inhibition Unleashes Antitumor Immunity in Colorectal Cancer by Activating the cGAS‐STING Pathway (from oncology)
L. Huo; Chong Wu; Xiaobo Li; Caina Ma; Jiaming Huang — Advanced Science 2026
Score: 4/10 | Pathways: cGAS-STING, other

This paper activates cGAS-STING via cytosolic DNA from genomic instability (HR deficiency), which shares the cGAS-STING-type I interferon axis central to the SAMHD1 mechanism, but the driver is nuclear DNA damage rather than dNTP pool dysregulation or mtDNA escape, and the clinical context (CRC immunotherapy sensitization) is only tangentially related to the SAMHD1 interferonopathy syndrome.
DOI: 10.1002/advs.202522826

Biomimetic Iridium‐Based Photothermal Nanozyme to Trigger Ferroptosis and Pyroptosis and Activate the cGAS‐STING Pathway for Improved Tumor Immunotherapy (from Oncology/Nanomedicine)
Lijun Ding; Zhongxiong Fan; Guoyu Xia; Fukai Zhu; N. Yang — Advanced Science 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, other

This oncology nanomedicine paper deliberately induces mtDNA oxidative damage and cGAS-STING activation as a therapeutic mechanism for tumor immunotherapy, touching on core pathways (cGAS-STING, pyroptosis/NLRP3, mtDNA release) relevant to the SAMHD1 disease model, but entirely in an artificial photothermal/ROS cancer context with no connection to SAMHD1 haploinsufficiency, interferonopathy, or the family phenotype.
DOI: 10.1002/advs.202519186

Leveraging Naturally Assembled Tumor Extracellular Vesicles as Self-Adjuvanting Nanovaccines to Potentiate Cancer Immunotherapy via cGAS/STING Activation. (from Oncology/nanomedicine)
Jianing Gong; K. Liang; Yinzhe Sun; Laozhi Xie; Yukun Huang — ACS nano 2026
Score: 3/10 | Pathways: cGAS-STING, other

This paper exploits cGAS/STING activation as a cancer immunotherapy tool using engineered extracellular vesicles, which is mechanistically adjacent to the BLUE stream of the disease profile but is focused on therapeutic oncology engineering rather than providing any mechanistic insight into SAMHD1 haploinsufficiency, interferonopathy, or the pathological consequences of dysregulated cGAS-STING signaling relevant to the family phenotype.
DOI: 10.1021/acsnano.5c15637

Pathway Coverage This Week

  • cGAS-STING: 37 papers
  • treatment-target: 22 papers
  • other: 20 papers
  • JAK-STAT: 20 papers
  • POLG-mtDNA: 12 papers
  • IRF7-metabolic: 12 papers
  • VDAC1: 11 papers
  • NLRP3: 9 papers
  • BIK-cancer: 7 papers
  • ME-CFS: 6 papers
  • AGS-spectrum: 4 papers
  • mTOR-lysosomal: 4 papers
  • clinical-phenotype: 4 papers
  • ISG15-mitophagy: 2 papers

SAMHD1 Research Digest — 2026-04-26

Generated by samhd1_monitor | Model: claude-sonnet-4-6

Summary: 10 papers evaluated | 4 high-relevance (≥7) | 5 medium (5–6) | 1 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Added to Zotero automatically

TH5487 specifically targets NLRP3 in FCAS patients resistant to MCC950. (from Autoinflammatory/rare disease (FCAS - Familial Cold Autoinflammatory Syndrome))
Lackner Angela; Picucci Sofia I; Jiang Wenjin; Onyuru Janset; Campos Melissa — 2026
Score: 8/10 | Pathways: NLRP3, POLG-mtDNA, cGAS-STING, treatment-target, ME-CFS

This paper directly addresses NLRP3 inflammasome inhibition via a novel hOGG1/oxidized-mtDNA sensing mechanism, demonstrates cryo-EM evidence of NLRP3-mitochondrial DNA association, shows TH5487 works where MCC950 fails (critical for treatment-resistant cases), and reveals that NLRP3 inhibition simultaneously increases type I interferon responses—all highly relevant to the PURPLE and BLUE pathways of the SAMHD1 haploinsufficiency mechanism where ox-mtDNA drives NLRP3 activation (Loop B) and cGAS-STING drives IFN-I (Loop A).
DOI: 10.1038/s42003-026-10008-2

Sesamin ameliorates high-fat diet-induced inflammation and metabolic dysfunction in pregnant uterine smooth muscle via cGAS-STING inhibition. (from Obstetrics/maternal-fetal medicine)
Xu Chenyi; Li Xuan; Yang Chen; Xing Ting; Yang Longtao — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, pregnancy-fetal, treatment-target, IRF7-metabolic

This paper directly demonstrates the mtDNA leakage → cGAS-STING → IL-1β/IL-18 axis in a metabolic-inflammatory context with mitochondrial dysfunction, and identifies sesamin as a STING inhibitor that blocks this pathway — mechanistically overlapping with the BLUE and PURPLE streams of the SAMHD1 syndrome, while the pregnancy/uterine context is relevant to the obstetric phenotype dimension of the family.
DOI: 10.1016/j.phymed.2026.158182

TREM2 & senescent macrophages fuel inflammaging and metabolic dysfunction-associated steatotic liver disease. (from Hepatology/Geroscience)
Salladay-Perez Ivan A; Avila Itzetl; Estrada Lizeth; Alexandru Andreea C; Ponce * — 2026
Score: 7/10* | Pathways: cGAS-STING, NLRP3, VDAC1, JAK-STAT, IRF7-metabolic, POLG-mtDNA, mTOR-lysosomal, clinical-phenotype, treatment-target

This paper directly demonstrates that cytosolic mitochondrial DNA drives type I interferon signaling in senescent macrophages causing MASLD and inflammaging—mechanistically overlapping with the BLUE (cGAS-STING via mtDNA escape) and GOLD (liver/metabolic) streams of the SAMHD1 A565T syndrome, and the hepatic steatosis and cholecystectomy clustering phenotypes tracked in the family, with senolytic treatment as a novel therapeutic angle.
DOI: 10.1038/s43587-026-01101-6

Efficacy of JAK1/2 inhibitors in AGS genes-related interferonopathies: A multicenter retrospective observational study with treated vs untreated comparison. (from Pediatric neurology / rare disease genetics)
G. Marinella; Ylenia Vaia; Davide Politano; J. Galli; F. Nicita — Molecular genetics and metabolism 2026
Score: 7/10 | Pathways: JAK-STAT, AGS-spectrum, treatment-target, cGAS-STING, ISG15-mitophagy, ME-CFS, clinical-phenotype

This multicenter retrospective study directly evaluates baricitinib and ruxolitinib (JAK1/2 inhibitors) in AGS-related type I interferonopathies—the same therapeutic class most relevant to SAMHD1 haploinsufficiency-driven IFN-I overproduction—and critically notes that pathogenetic complexity extends beyond JAK-STAT, implying residual disease burden from parallel NLRP3/VDAC1/ISG15 streams that mirror the multi-loop mechanism of the documented family syndrome.
DOI: 10.1016/j.ymgme.2026.109907

🟡 Medium Relevance (Score 5–6)

Review and add to Zotero manually if warranted

MRE11A Regulates Sepsis Through the mtDNA/STING Pathway of T Lymphocyte Apoptosis (from Pediatric critical care / sepsis immunology)
Wei Zhixin; Wang Feifei; Qin Pengji; Yang Zhiyong — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, ME-CFS, other

This paper directly demonstrates the mtDNA-cytosol → cGAS → STING axis driving T lymphocyte apoptosis via MRE11A loss, mechanistically paralleling the BLUE stream in SAMHD1 haploinsufficiency where cytosolic mtDNA fragments activate cGAS-STING-IRF3-IFN-I, with the added implication that MRE11A-mediated mtDNA containment failure (analogous to VDAC1 macropore-driven mtDNA escape) amplifies cGAS-STING signaling and immune exhaustion relevant to post-viral ME/CFS and immunodysfunction phenotypes in the family.
DOI: 10.21203/rs.3.rs-9414184/v1

18-β-glycyrrhetinic acid facilitates nuclear-mitochondrial communications to alleviate oxidative stress through HMGB1-cGAS-Mul1 axis in tendinopathy. (from Orthopaedics/musculoskeletal biology)
Gao Yuan-Yuan; Sun Wen-Shuang; Sun Zi-Ying; Wang Jun-Rui; Lv Zhong-Yang — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target, other

This paper directly characterizes a novel cGAS degradation mechanism via Mul1 ubiquitin ligase and HMGB1 methylation that suppresses cGAS-STING-NLRP3 signaling under oxidative stress—highly relevant as a potential therapeutic axis for the BLUE and PURPLE streams of the SAMHD1 haploinsufficiency syndrome, though the clinical context (tendinopathy) is entirely orthogonal to the family phenotype.
DOI: 10.1186/s12967-026-08091-4

Towards effective targeted therapies in morphea. (from Dermatology)
Amanda M Saracino; L. Iyengar; M. Nikpour — Italian journal of dermatology and venereology 2026
Score: 6/10 | Pathways: JAK-STAT, AGS-spectrum, cGAS-STING, treatment-target, clinical-phenotype

Morphea is characterized here as a type I interferonopathy enriched for IFN-I pathways, directly overlapping the BLUE/RED streams of the SAMHD1 mechanism, and JAK inhibitors (baricitinib, ruxolitinib class) are flagged as emerging treatments—the same class relevant to managing SAMHD1-driven interferonopathy—making this an adjacent clinical phenotype with shared molecular architecture and therapeutic implications.
DOI: 10.23736/S2784-8671.25.08413-0

Targeting cytokine pathways: the role of biologics in autoinflammatory disorders (from Rheumatology/rare disease)
T. Koga — Expert Review of Clinical Immunology 2026
Score: 6/10 | Pathways: NLRP3, JAK-STAT, AGS-spectrum, treatment-target, clinical-phenotype, IRF7-metabolic

This review directly covers interferonopathies and inflammasomopathies including their molecular mechanisms (IL-1/NLRP3, JAK-STAT/type I IFN) and therapeutic targeting with JAK inhibitors and IL-1 biologics, which are directly relevant to the SAMHD1 haploinsufficiency syndrome's dual NLRP3 and type I interferonopathy streams and potential treatment strategies, though SAMHD1 itself is not mentioned.
DOI: 10.1080/1744666X.2026.2625277

Discovering patterns in the pathologic significance of non-missense deleterious variants in RELA. (from Clinical Immunology / Rare Autoinflammatory Disease)
H. Hayakawa; M. Tsumura; Takanori Utsumi; H. Nihira; Wei-Te Lei — The Journal of allergy and clinical immunology 2026
Score: 5/10 | Pathways: JAK-STAT, AGS-spectrum, clinical-phenotype, other

RELA haploinsufficiency vs. dominant-negative distinction with type I interferonopathy overlap is conceptually analogous to SAMHD1 haploinsufficiency mechanisms, and the identification of DN variants driving interferonopathy beyond HI phenotypes parallels the SAMHD1 heterozygous pathogenic framework, but RELA/NF-κB is a parallel inflammatory axis not directly in the SAMHD1 mechanistic streams (cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy).
DOI: 10.1016/j.jaci.2026.01.020

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Systematic discovery of pro- and anti-HIV host factors in primary human CD4+ T cells. (from virology)
Rathore Ujjwal; Dugan Eli; Thornton Hunter; Kumar Vigneshwari Easwar; Dajani Ram — 2026
Score: 3/10 | Pathways: dNTPase, other

This paper studies HIV host factors in CD4+ T cells using CRISPR screens and identifies restriction factors including cyclophilin paralogs and viral entry modulators, tangentially relevant only because SAMHD1 is a known HIV restriction factor (dNTPase/Vpx target) but the paper does not study SAMHD1, its dNTPase activity, or any of the core cGAS-STING/NLRP3/mitochondrial pathways relevant to the A565T haploinsufficiency syndrome.
DOI: 10.1016/j.cell.2026.03.046

Pathway Coverage This Week

  • cGAS-STING: 7 papers
  • treatment-target: 7 papers
  • NLRP3: 5 papers
  • JAK-STAT: 5 papers
  • clinical-phenotype: 5 papers
  • POLG-mtDNA: 4 papers
  • AGS-spectrum: 4 papers
  • other: 4 papers
  • ME-CFS: 3 papers
  • IRF7-metabolic: 3 papers
  • pregnancy-fetal: 1 papers
  • VDAC1: 1 papers
  • mTOR-lysosomal: 1 papers
  • ISG15-mitophagy: 1 papers
  • dNTPase: 1 papers