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ISG15-mitophagy

SAMHD1 Research Digest — 2026-09-13

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 29 papers evaluated | 6 high-relevance (≥7) | 12 medium (5–6) | 11 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses (from cell biology/organelle biology review)
Zhuo-Er Li; Chunli Wang; Jin-Rong Zhang; Zhi-Qiang Guo — Frontiers in Immunology 2026
Score: 8/10 | Pathways: ISG15-mitophagy, cGAS-STING, JAK-STAT, treatment-target

This review directly addresses the RED pathway mechanism (ISG15/ISGylation of MFN1/MFN2 blocking mitophagy) that is central to the SAMHD1 A565T mitochondrial-interferon convergence model, including STING and mitophagy crosstalk relevant to disease pathogenesis.
DOI: 10.3389/fimmu.2026.1960492

Mitochondrial Fis1 tunes Rab7A activity via TBC1D15 modulating STING degradation. (from Cell biology/mitochondrial trafficking)
— Cell reports 2026
Score: 7/10** | Pathways: cGAS-STING, treatment-target

Identifies a novel mitochondria-lysosome trafficking axis (Fis1-TBC1D15-Rab7A) controlling STING degradation and signal termination, directly relevant to the chronic/unresolved IFN-I signaling (Loop A/RED) implicated in the SAMHD1 A565T interferonopathy.
DOI: 10.1016/j.celrep.2026.117994

Precision tuning of STING signaling: a mutational blueprint (from structural biology / high-throughput functional genomics)
— Signal Transduction and Targeted Therapy 2026
Score: 7/10** | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

This comprehensive mutational atlas of STING signaling directly maps the structural determinants of IFN-I induction and NF-κB activation downstream of cGAS-STING, a core pathway (BLUE stream) driving the interferon-mitochondrial syndrome in SAMHD1 A565T haploinsufficiency, and offers therapeutic modulation insights applicable to future STING antagonist strategies for this family.
DOI: 10.1038/s41392-026-02968-y

Mitochondria-Targeted Multimodal Nanotherapeutics Suppress Oxidized mtDNA-Driven Inflammation at the Source. (from Nanomedicine/pulmonology (ARDS))
Li Wen-Ling; Cao Juan; Wang Yu-Lin; Fan Yu-Han; Xu Jia-Qi — 2026
Score: 7/10 | Pathways: VDAC1, NLRP3, treatment-target, POLG-mtDNA

This nanotherapeutic directly targets oxidized mtDNA leakage and downstream inflammation at the mitochondrial source, a core mechanism (Loop A/B) in SAMHD1 A565T pathology, offering a plausible therapeutic strategy analogous to VBIT-4/MCC950 for the interferon-mitochondrial syndrome.
DOI: 10.1002/advs.77577

Lipotoxicity-induced ER-mitochondrial hypercoupling activates the mtDNA-cGAS-STING-NF-κB axis to drive follicular arrest in metabolically compromised PCOS (from Reproductive endocrinology/gynecology (PCOS))
— Cell Death Discovery 2026
Score: 7/10** | Pathways: cGAS-STING, NF-kB-IKK, treatment-target, clinical-phenotype

Demonstrates mPTP-mediated mtDNA release activating cGAS-STING-NF-κB inflammatory cascade, directly paralleling the BLUE-loop/NF-κB crosstalk mechanism central to the SAMHD1 interferon-mitochondrial model, with therapeutic parallels (STING/ER stress inhibitors, melatonin) relevant to treatment translation.
DOI: 10.1038/s41420-026-03339-w

Mitochondria in SARS-CoV-2 infection: Immune interactions and molecular approaches in the Post COVID-19 condition. (from Virology/Post-viral syndrome (Post-COVID condition))
Barros Maria Clara; Souza Felipe Gouvêa de; Costalat Helenize; Pinho Catarina To — 2026
Score: 7/10 | Pathways: NLRP3, mito-ROS-NF-kB, ISG15-mitophagy, ME-CFS, clinical-phenotype

This review covers SARS-CoV-2-induced mitochondrial dysfunction, ROS-driven NLRP3 activation, mitophagy impairment, and post-COVID sequelae, directly paralleling the proband's viral-triggered ME/CFS and the interferon-mitochondrial convergence mechanism central to the SAMHD1 A565T phenotype.
DOI: 10.1590/1678-4685-gmb-2025-0118

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

The interaction between HIV-1 central polypurine tract and host SAMHD1 dNTPase during HIV-1 vector transduction in human primary nondividing monocyte-derived macrophages. (from Virology/gene therapy vector engineering)
Alvarez Natalie N; Burke Hannah S; Freeman Tzipporah; Taki Sara; Li Qun — Virus genes 2026
Score: 6/10 | Pathways: dNTPase, treatment-target

Directly studies SAMHD1 dNTPase activity and Vpx-mediated degradation in macrophages, providing mechanistic insight into the core dNTP pool pathway relevant to A565T haploinsufficiency, though focused on viral restriction/vector transduction rather than the interferonopathy phenotype.
DOI: 10.1007/s11262-026-02272-5

Redox-driven mitochondrial DNA stress in hepatocellular carcinoma: innate immune remodelling, tumour immune escape, and immunotherapy implications (from Hepatology/Oncology)
Ze Chang; Guan-Nan Liu; Jin-Shan Zhang; Hai-Lin Lei; Hai-Yan Quan — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target

Paper details mtDNA release mechanisms (oxidation, cGAS-STING, TLR9, NLRP3/TFAM coupling) directly parallel to the BLUE/PURPLE loops in the SAMHD1 mechanism, though in an HCC oncology context rather than SAMHD1 haploinsufficiency.
DOI: 10.3389/fimmu.2026.1903643

Colchicine-related effects on gene and protein expression in gout. (from Rheumatology)
Mitchell Will T; Wheeler Austin M — Current opinion in rheumatology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Colchicine's mechanism via NLRP3 inhibition and MSU-driven inflammation directly overlaps with the GOLD pathway (dGTP→uric acid→MSU crystals→NLRP3) and offers a potential treatment lead relevant to the SAMHD1 A565T inflammasome hyperactivation phenotype.
DOI: 10.1097/BOR.0000000000001192

Mitochondrial Transplantation Suppresses mtDNA-cGAS/STING-Mediated Innate Immunity by Enhancing PINK1/Parkin-Dependent Mitophagy to Attenuate Keloid Fibrosis (from dermatology/plastic surgery (keloid fibrosis))
Wen-Jing Wang; Yuan-Bo Liu; Ji-Peng Song; Zou-Zou Yu; Zi-Xian Chen — Antioxidants 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, treatment-target

Demonstrates mtDNA leakage driving cGAS/STING activation via impaired PINK1/Parkin mitophagy in fibrosis, directly paralleling the BLUE/RED loops of SAMHD1-related interferonopathy though in a dermatologic keloid model rather than SAMHD1 haploinsufficiency.
DOI: 10.3390/antiox15091120

Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration. (from neurology/neurodegeneration)
Basak Bishal; Riley Julia F; Nataraj Neha M; Holzbaur Erika Lf — 2026
Score: 6/10 | Pathways: ISG15-mitophagy, NF-kB-IKK, treatment-target, other

Reviews PINK1/Parkin mitophagy pathways and their links to NF-κB and cGAS-STING neuroinflammation, directly relevant to the RED loop mitophagy block and neuroinflammatory mechanisms in the SAMHD1 model though not SAMHD1-specific.
DOI: 10.1172/jci199847

STC1 promotes monosodium urate crystal-induced gouty inflammation via the cAMP-PKA-NF-κB/NLRP3 pathway in mice. (from Rheumatology (gouty arthritis))
He Yue; Zheng Hui; Yue Zhi; Ge Tingqiu; Hu Yanqing — Cellular signalling 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, NF-kB-NLRP3-priming, mito-ROS-NF-kB

Demonstrates MSU crystal-driven NLRP3/NF-κB inflammasome activation via cAMP-PKA and mitochondrial ROS, directly paralleling the GOLD (urate-NLRP3) and mito-ROS-NF-κB axes implicated in SAMHD1 dGTP-driven purine catabolism pathology, though not SAMHD1-specific.
DOI: 10.1016/j.cellsig.2026.112862

Genomic Structural Equation Modeling Identifies a Shared Inflammatory Genetic Dimension Across Inflammatory Arthritis Phenotypes and Biomarkers. (from statistical genetics/rheumatology)
Feng Xiaojian; Pan Zhixian; Liu Guoping — Annals of human genetics 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, clinical-phenotype, NF-kB-NLRP3-priming

This genomic SEM study converges on NLRP3, urate, and IL6R pathways underlying rheumatoid arthritis, psoriatic arthritis, and gout, directly paralleling the GOLD-stream uric acid/NLRP3 axis and RA/PsA phenotypes documented in the SAMHD1 family.
DOI: 10.1111/ahg.70058

The Secretome Derived From Human Umbilical Cord Mesenchymal Stem Cells Improves Skin Photoaging by Enhancing Mitophagy to Inhibit the cGAS-STING Pathway. (from Dermatology/regenerative medicine (stem cell secretome therapy))
Tang Tingting; Lin Meifen; Yang Jingjing; Yang Xinyu; Xu Xunhong — 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, treatment-target

Demonstrates mitophagy-mediated suppression of mtDNA leakage and cGAS-STING/IFN-β activation, directly relevant to the BLUE/RED mechanistic loops in SAMHD1 haploinsufficiency though applied to a dermatologic aging model rather than SAMHD1 itself.
DOI: 10.1111/acel.70701

The GPX3-VCAM1 Axis Gates Pro-Fibrotic Tubule Cell Fate in Hyperuricemic Nephropathy. (from Nephrology)
Qi Yunfei; Zhao Qiang; Lve Yue; Yuan Yaming; Zhou Tingting — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 5/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Demonstrates soluble uric acid activating renal NLRP3 inflammasome to drive fibrosis, paralleling the GOLD dGTP-to-uric-acid-to-NLRP3 pathway in the SAMHD1 mechanism, though in a distinct hyperuricemic nephropathy context without SAMHD1 involvement.
DOI: 10.1002/advs.77676

The Significance of cGAS-STING Signaling in Response to Oncogenic Viruses. (from Oncology/Virology)
Guo Limei; Li Li; Wang Fang; Liu Wen; Zhang Yan — 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target

General review of cGAS-STING pathway in oncogenic virus-driven cancers provides background on the core BLUE-loop signaling axis but has no direct connection to SAMHD1, mitochondrial dNTP dysregulation, or the described family phenotype.
DOI: 10.1002/cbf.70296

Glutathione reductase deficiency potentiates the immunogenicity of ferroptosis and cuproptosis via amplified reactive oxygen species accumulation and cGAS-STING pathway activation. (from Oncology (cancer immunotherapy/redox biology))
Deng Xiaoyi; Deng Zaidong; Zhu Bin; Hu Ruiqi; Ma Jing — 2026
Score: 5/10 | Pathways: cGAS-STING, other

Demonstrates mitochondrial DNA release triggering cGAS-STING via oxidative/mitochondrial stress in cancer cells, a mechanism parallel to the BLUE loop in SAMHD1 pathology though in an oncology/ferroptosis context rather than SAMHD1 haploinsufficiency.
DOI: 10.1186/s13045-026-01840-4

Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems. (from gene therapy / RNA delivery engineering)
Lei Xinlin; Chen Didi; Zhang Kun; Liu Xiyu; Chen Qiubing — Nature biomedical engineering 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper describes a generalizable LNP/pegRNA delivery advance for in vivo prime editing that is relevant as a future therapeutic correction strategy for a heterozygous missense variant like SAMHD1 p.A565T, though it demonstrates only liver hepatocyte editing rather than immune/myeloid cells.
DOI: 10.1038/s41551-026-01787-4

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Navigating off-target effects in CRISPR-based genome editing for safer gene therapies (from genome editing / gene therapy engineering)
— Discover Genetics and Evolution 2026
Score: 4/10** | Pathways: prime-editing, gene-therapy-delivery

General CRISPR off-target review relevant to future gene correction strategies for SAMHD1 variants but lacks disease-specific or pathway-specific content.
DOI: 10.1007/s00294-026-01339-y

Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2 (from gene editing / genomics methodology)
Tingting Cong; Run-Da Xu; Xuan-Cheng Chen; Jun-Song Yuan; Zuo-Miao Lin — Nature Communications 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper presents an off-target detection method for CRISPR editors relevant to future gene correction of missense variants like A565T, but has no direct connection to SAMHD1 biology or the interferon-mitochondrial pathway.
DOI: 10.1038/s41467-026-76778-9

Post-translational control of MAVS signaling: linking mitochondrial antiviral immunity to metabolic and cellular stress contexts (from virology/biochemistry of mitochondrial signaling)
Nao Morimoto; Tomohiko Okazaki — Frontiers in Physiology 2026
Score: 4/10 | Pathways: cGAS-STING, other

MAVS/RLR pathway is a parallel mitochondrial-innate immune signaling axis distinct from but conceptually adjacent to the cGAS-STING/IFN-I pathway central to SAMHD1 interferonopathy, without direct SAMHD1 or NLRP3/VDAC1/ISG15 mechanistic overlap.
DOI: 10.3389/fphys.2026.1907325

Itaconate and its derivatives in human health and diseases. (from immunometabolism)
Gu Jianyou; Zhang Wenying; Zhang Junfeng; Zeng Silue; Xia Renpei — 2026
Score: 3/10 | Pathways: NLRP3, other

This is a general review of itaconate/IRG1-ACOD1 immunometabolism with tangential relevance to NLRP3-driven inflammation but no direct connection to SAMHD1, dNTPase, cGAS-STING, or mitochondrial dNTP transport pathways central to this disease.
DOI: 10.1038/s41392-026-02936-6

Tumor microenvironment and signaling pathways in melanoma brain metastasis. (from Oncology/neuro-oncology)
Rosell Rafael; González-Cao María; Olmo-González Daniel; Hold Emilia; Molina-Vil — Annals of translational medicine 2026
Score: 3/10 | Pathways: cGAS-STING, other

This melanoma brain metastasis review touches on cGAS-STING/TBK1 and mitochondrial dysfunction mechanisms but is focused on oncology/tumor microenvironment unrelated to SAMHD1 A565T pathophysiology.
DOI: 10.21037/atm-2026-0127

Context-dependent roles of cGAS-STING signaling in glioblastoma: Therapeutic resistance, drug delivery, and heterogeneity-informed translation. (from Neuro-oncology)
— Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2026
Score: 3/10** | Pathways: cGAS-STING, NF-kB-IKK

This is a glioblastoma-focused oncology review discussing cGAS-STING/NF-kB signaling in tumor context, with no direct connection to SAMHD1, its mechanistic pathways, or the family phenotype spectrum.
DOI: 10.1016/j.biopha.2026.119915

Elucidate the structural role of helper lipids in modulating hepatic expression following repeated intravenous administration of mRNA-LNPs (from pharmaceutical sciences/nanomedicine drug delivery)
Jia-Hao Ge; Xiaochen Bo; Xinye Zhu; M. Long; Yi-Qing Zhang — Materials Today Bio 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper concerns mRNA-LNP formulation for hepatic protein delivery and gene editing, with only tangential relevance via IL-6/inflammation induction by lipid components, not directly connected to SAMHD1 or the core interferon-mitochondrial pathways.
DOI: 10.1016/j.mtbio.2026.103621

Twelve Japanese patients with POLG-related disorders: Population-specific genetic differences of POLG variants in Japan and Europe. (from Clinical genetics/mitochondrial medicine (pediatric neurology))
Ueda Nahoko Katayama; Mimaki Masakazu; Wang Zhaoxia; Mizuno Yoko; Namai Yoshiyuk — Brain & development 2026
Score: 3/10 | Pathways: POLG-mtDNA

This paper concerns POLG mutation epidemiology in classic mitochondrial disease (PEO, mtDNA deletions) in Japanese patients, not related to SAMHD1 pathway or interferon-mitochondrial crosstalk, though POLG stalling is a downstream node in the PURPLE loop.
DOI: 10.1016/j.braindev.2026.104590

Factors associated with hyperuricemia in overweight or obese adults of Shenzhen, China. (from Epidemiology/Endocrinology)
Tang Leyao; Dai Wenjie; Xiong Ni; Liang Liping; Wu Xin Yin — 2026
Score: 3/10 | Pathways: urate-NLRP3

This is a population epidemiology study on hyperuricemia risk factors in obesity unrelated to SAMHD1 mechanisms, only tangentially touching the GOLD pathway (dGTP→uric acid→NLRP3) via urate biology without any mechanistic or genetic link.
DOI: 10.1038/s41598-026-68519-1

Autoimmunity: Molecular Mechanisms, Biomarkers, and Therapeutic Opportunities. (from General rheumatology/autoimmunity review)
Kuang Jialong; Zhu Yin; Xu Fang; Liu Yongjing; Li Yuan — 2026
Score: 3/10 | Pathways: JAK-STAT, treatment-target, other

This is a broad general review of autoimmune disease mechanisms (immunometabolism, epigenetics, RNA regulation) without any specific mention of SAMHD1, cGAS-STING, NLRP3, interferonopathy, or mitochondrial dNTP pathways central to the SAMHD1 A565T syndrome.
DOI: 10.1002/mco2.70905

WEAK IMMUNITY DURING INSOMNIA (from Sleep medicine)
— Special journal of the Medical Academy and other Life Sciences 2026
Score: 3/10** | Pathways: ME-CFS, clinical-phenotype

This low-quality, non-peer-reviewed-looking survey on insomnia and immunity mentions mitochondrial dysfunction and ME/CFS tangentially but provides no mechanistic data on SAMHD1, interferon, or inflammasome pathways relevant to the family syndrome.
DOI: 10.58676/sjmas.v4i8.190

Pathway Coverage This Week

  • treatment-target: 14 papers
  • cGAS-STING: 12 papers
  • NLRP3: 8 papers
  • other: 6 papers
  • ISG15-mitophagy: 5 papers
  • urate-NLRP3: 5 papers
  • NF-kB-IKK: 4 papers
  • clinical-phenotype: 4 papers
  • gene-therapy-delivery: 4 papers
  • mito-ROS-NF-kB: 3 papers
  • prime-editing: 3 papers
  • JAK-STAT: 2 papers
  • POLG-mtDNA: 2 papers
  • ME-CFS: 2 papers
  • NF-kB-NLRP3-priming: 2 papers
  • VDAC1: 1 papers
  • dNTPase: 1 papers

SAMHD1 Research Digest — 2026-09-09

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 13 papers evaluated | 1 high-relevance (≥7) | 6 medium (5–6) | 6 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Metabolic regulation of mitochondrial DNA (mtDNA) homeostasis. (from mitochondrial biology/metabolism)
Medeiros Tania Catarina; Calabrese Gaetano — Biochimica et biophysica acta. Molecular cell research 2026
Score: 7/10 | Pathways: POLG-mtDNA, mito-dNTP-transport, nucleotide-rewiring, dNTPase

This review directly addresses mitochondrial nucleotide pool regulation and POLG-driven mtDNA replication/quality control, mechanistically central to the PURPLE/GOLD streams of dGTP-driven mitochondrial dysfunction in SAMHD1 haploinsufficiency.
DOI: 10.1016/j.bbamcr.2026.120220

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

The Oxidative–Mitochondrial–Inflammatory Axis in Retinitis Pigmentosa: Extracellular mtDNA as Biomarker and Therapeutic Read-Out (from Ophthalmology (retinitis pigmentosa))
— Antioxidants 2026
Score: 6/10** | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target

This review details mtDNA release-driven cGAS-STING/TLR9/NLRP3 neuroinflammation via oxidative-mitochondrial dysfunction, directly paralleling the BLUE/PURPLE loops in SAMHD1 pathology though in a distinct retinal degeneration context.
DOI: 10.3390/antiox15091110

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: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, ISG15-mitophagy, clinical-phenotype

Details mitophagy/autophagy failure, mtDNA/DAMP release, and NLRP3-driven pyroptosis in cardiovascular inflammation, directly paralleling the mitochondrial-NLRP3-IL-1β mechanistic axis relevant to the SAMHD1 interferon-mitochondrial syndrome's cardiac phenotype risk.
DOI: 10.1097/crd.0000000000001302

Organelle-orchestrated cGAS-STING signaling and its role in neurodegeneration. (from Neurodegeneration/organelle biology)
Jin-Yue Liu; Sheng-ye Liu; Li-Xian Ran; Wenhao Qiao; Fan Zhang — Pharmacological research 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

This review details organelle regulation of cGAS-STING (mitochondria, ER, MAMs, Golgi, lysosomes) and its role in chronic neuroinflammation, directly relevant to the BLUE loop mechanism (VDAC1/mtDNA/cGAS/STING/IFN-I) underlying the SAMHD1 A565T interferonopathy and its neurologic/AuDHD phenotypes, though it does not address SAMHD1 or NLRP3/NF-kB crosstalk directly.
DOI: 10.1016/j.phrs.2026.108216

Peroxiredoxin 6 limits mitochondrial peroxidation to prevent mitochondrial ER contact site assembly and inflammatory signalling following adaptive stress (from muscle physiology/redox biology)
PengLin Li; Yating Zheng; Jiwang Tang; Qin Xia; José C Casas-Martinez — bioRxiv 2026
Score: 6/10 | Pathways: VDAC1, NLRP3, mito-ROS-NF-kB, treatment-target

Demonstrates mitochondrial lipid peroxidation driving mtDNA release via MERCS/calcium dysregulation and innate immune activation, mechanistically paralleling the VDAC1-mtDNA-cGAS/NLRP3 axis central to SAMHD1 haploinsufficiency pathology even though SAMHD1 itself is not studied.
DOI: 10.64898/2026.07.24.740509

p300 Degradation by the p53-SIAH1 Axis Relieves TBK1 Acetylation to Enhance Innate Antiviral Immunity. (from virology/molecular oncology (p53-SIAH1-p300 axis in antiviral immunity))
Yu Huidi; Zhan Zhihao; Pan Xiaoxiang; Zhang Xinyue; Liu Penggang — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Identifies p300-mediated TBK1 acetylation as a brake on IRF3-driven type I IFN production, directly relevant to the BLUE cGAS-STING-IRF3-IFN loop and NF-kB/IKK crosstalk central to the SAMHD1 interferonopathy model, though not SAMHD1-specific.
DOI: 10.1002/advs.76101

Next-Generation Genome Editing: Overcoming CRISPR-Cas9 Limitations with Prime Editing and PASTE Technology (from gene therapy/genome engineering)
Vikash Kumar; Aman Kumar; Balak Das Kurmi — Current Pharmacogenomics and Personalized Medicine 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

General review of prime editing and PASTE technology relevant as a future correction strategy for a heterozygous missense variant like SAMHD1 A565T, but does not address SAMHD1 or its mechanisms directly.
DOI: 10.2174/0118756921492763260804044215

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Cell-Free Mitochondrial DNA as a Damage-Associated Molecular Pattern and Candidate Biomarker in Sickle Cell Disease Vaso-Occlusive Crisis: A Scoping Review (from Hematology (sickle cell disease))
Amoako Jerriod Paul Amoako; Owusu-Andoh Alexis; PSVV Charan; Atta-Poku Doris Ewu — 2026
Score: 4/10 | Pathways: cGAS-STING, VDAC1, clinical-phenotype

This scoping review discusses cf-mtDNA as a DAMP activating cGAS-STING-TBK1 in sickle cell vaso-occlusive crisis, mechanistically parallel to the BLUE loop but in a distinct disease with no SAMHD1 connection.
DOI: 10.21203/rs.3.rs-10864540/v1

ZBP1-mediated sensing of genomic stress in cancer therapy (from Oncology/cell death biology)
Xiao Zhong; Siddharth Balachandran; Ting Zhang — Ferroptosis and Oxidative Stress 2026
Score: 3/10 | Pathways: other

ZBP1/necroptosis/RIPK3 cancer-therapy pathway is a distinct innate nucleic-acid sensing axis with only tangential overlap (Z-RNA/R-loop stress) to SAMHD1's cGAS-STING/NLRP3/mitochondrial mechanisms, and no direct SAMHD1 or family-phenotype connection.
DOI: 10.70401/fos.2026.0035

Somatic Genome Editing in Cardiovascular Disease: Platforms, Targets, and Translational Progress (from cardiology/gene therapy)
Khawli George; Gorini Francesca; Palazzo Mariangela; Daher Jalil; Borghini Andre — preprint (preprint) 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general review of somatic genome-editing platforms for cardiovascular disease (liver PCSK9/ANGPTL3/TTR, myocardial MYH7/MYBPC3) with no connection to SAMHD1, interferon/inflammasome pathways, or myeloid/immune cell correction strategies relevant to A565T.
DOI: 10.20944/preprints202609.0314.v1

Cascade-catalytic microneedles convert the tumor cholesterol shield into an oxidative spear for self-amplifying ferroptosis-driven cancer immunotherapy. (from Oncology/nanomedicine biomaterials engineering)
Rongjie Yang; Yu Zhang; Yushu Dong; Shuiling Chen; Ming Li — Biomaterials 2026
Score: 3/10 | Pathways: cGAS-STING

This paper uses cGAS-STING activation as a downstream immunotherapy mechanism in cancer nanomedicine, but is unrelated to SAMHD1 biology, dNTP metabolism, or the interferon-mitochondrial syndrome described in the disease profile.
DOI: 10.1016/j.biomaterials.2026.124474

From immune dysregulation to renal injury: mechanistic insights and translational opportunities in immune-mediated nephropathies. (from Nephrology)
Xiaoming Wang — Frontiers in cell and developmental biology 2026
Score: 3/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, NF-kB-IKK, other

This nephrology review discusses cGAS-STING, NLRP3, NF-κB, and JAK-STAT pathways generically in immune-mediated kidney disease but has no direct connection to SAMHD1, its variants, or the documented family phenotypes.
DOI: 10.3389/fcell.2026.1878787

Single-Cell and Spatial Transcriptomics Define Eosinophil Heterogeneity during Influenza A Virus-induced Exacerbation of Fungal Allergic Asthma in C57BL/6 mice. (from pulmonology/immunology (allergic asthma and influenza))
Veltri Anthony J; Wells Anthony J; Baus Magdaline; Mathur Sameer K; Samarasinghe — Journal of leukocyte biology 2026
Score: 3/10 | Pathways: JAK-STAT, other

Samhd1 appears only as one of many interferon-stimulated genes noted in a mouse eosinophil single-cell transcriptomics study of flu/asthma, with no mechanistic or clinical link to SAMHD1 haploinsufficiency or the syndrome described.
DOI: 10.1093/jleuko/qiag120

Pathway Coverage This Week

  • cGAS-STING: 6 papers
  • NLRP3: 4 papers
  • treatment-target: 4 papers
  • other: 3 papers
  • POLG-mtDNA: 2 papers
  • mito-ROS-NF-kB: 2 papers
  • clinical-phenotype: 2 papers
  • VDAC1: 2 papers
  • NF-kB-IKK: 2 papers
  • prime-editing: 2 papers
  • gene-therapy-delivery: 2 papers
  • JAK-STAT: 2 papers
  • mito-dNTP-transport: 1 papers
  • nucleotide-rewiring: 1 papers
  • dNTPase: 1 papers
  • ISG15-mitophagy: 1 papers

SAMHD1 Research Digest — 2026-09-02

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 8 papers evaluated | 2 high-relevance (≥7) | 4 medium (5–6) | 2 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Reprogramming Autoimmune Immunity via Mitochondrial Quality Control: Mechanisms, Biomarkers, and Windows for Intervention. (from Rheumatology/Autoimmunity)
Chen Xiao; Ding Jie; Meng Liu-Qing; Li Shu-Fang; Chen Yong — International immunopharmacology 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, ISG15-mitophagy, treatment-target, NF-kB-NLRP3-priming

This review directly discusses mitophagy/mtDNA-driven cGAS-STING-IFN-I amplification and NLRP3 hyperactivation as autoimmune drivers, mirroring the SAMHD1 A565T mitochondrial-interferon mechanism and proposing biomarker/treatment windows analogous to JAK inhibitor or MCC950-style interventions relevant to this family's phenotype.
DOI: 10.1016/j.intimp.2026.117316

Adipose-cartilage communication via EV-Mito-mtDNA signaling promotes osteoarthritis progression. (from Orthopedics/Rheumatology (osteoarthritis and obesity-adipose biology))
Gu Cheng; Liao Fawei; Kong Ganggang; Yin Shiyi; Jiang Yifei — 2026
Score: 7/10 | Pathways: cGAS-STING, mito-ROS-NF-kB, treatment-target

Demonstrates mtDNA (via EV transfer) activating cGAS-STING to drive inflammation and senescence, directly paralleling the BLUE loop (VDAC1-mtDNA-cGAS-STING-IFN) mechanism central to the SAMHD1 model, with therapeutic inhibition data.
DOI: 10.1126/sciadv.aee6780

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

Combined MEK1/2 and Autophagy Inhibition Suppresses Tumor Growth via STING-Mediated Type I Interferon Response in iCCA. (from Oncology (hepatobiliary cancer/MEK inhibitor pharmacology))
Sun Chengqiang; Gao Zheng; Dong Enfu; Ding Liangxia; Feng Shanru — Cancer science 2026
Score: 6/10 | Pathways: cGAS-STING, mTOR-lysosomal, ISG15-mitophagy, treatment-target

Demonstrates that autophagy/mitophagy suppresses cGAS-STING-TBK1 type I IFN signaling and that combined inhibition unleashes IFN-I output, directly modeling the mitophagy-IFN crosstalk (BLUE/RED loops) central to SAMHD1 pathology, though in an oncology (iCCA) rather than SAMHD1 context.
DOI: 10.1111/cas.70436

Neonatal Reversible Aortic Constriction Mice Model Unlocks Distinctive Footprints of Young Heart Recovery. (from Pediatric cardiology/cardiac surgery)
Huang Longming; Luo Kai; Zhang Xinjie; Zeng Guowei; Chen Bo — 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, treatment-target

This paper demonstrates the mtDNA-cGAS-STING pathway driving cardiac remodeling and shows mitophagy/urolithin A suppress STING activation, mechanistically paralleling the BLUE/RED loops in the SAMHD1 model and offering relevance to the cardiomyopathy/mitochondrial-cardiac phenotype tracked in the family, though it lacks any SAMHD1 connection.
DOI: 10.1161/jaha.125.047618

Uracil-DNA glycosylase 1 mitigates acute kidney injury inflammation by maintaining mtDNA homeostasis (from Nephrology)
xiaohui Liao; Wang Chunxia; Tang Wei; Xie Pan; Wang Yuting — 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, NF-kB-NLRP3-priming

Demonstrates mtDNA damage/leakage driving cGAS-STING inflammatory signaling in acute kidney injury via UNG1/SSBP1-mediated mtDNA repair, mechanistically parallel to the POLG-stalling/ox-mtDNA/cGAS-STING loop central to SAMHD1 A565T pathology though in a distinct disease context.
DOI: 10.21203/rs.3.rs-10469724/v1

Single-cell Unperturbed Activation Profiling by mass cytometry captures in vivo immune signaling in SLE. (from Rheumatology/single-cell mass cytometry biomarker methodology)
Burns Marie; Ostendorf Lennard; Abbas Amro; Ferrara Sebastian; Hirseland Heike — Frontiers in immunology 2026
Score: 5/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype

SLE study demonstrating type I IFN-driven pSTAT1/pSTAT3 signaling and baricitinib (JAK inhibitor) treatment monitoring is mechanistically relevant to the RED IFN-JAK-STAT pathway and JAK inhibitor therapeutics in the SAMHD1 interferonopathy model, though it does not involve SAMHD1 directly.
DOI: 10.3389/fimmu.2026.1844288

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Leukotrichia: A comprehensive review of follicular depigmentation. (from Dermatology)
Iamsumang Wimolsiri; Kositkuljorn Chaninan; Leerunyakul Kanchana; Sakpuwadol Naw — The Journal of international medical research 2026
Score: 4/10 | Pathways: poliosis-neural-crest, clinical-phenotype

This dermatology review on leukotrichia/piebaldism/Waardenburg-associated follicular depigmentation is tangentially relevant only insofar as it illuminates neural crest melanocyte biology underlying the family's tracked poliosis/silver-streak phenotype, with no direct SAMHD1 or interferon-mitochondrial pathway content.
DOI: 10.1177/03000605261483177

ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting. (from neurology/neuroimmunology)
Șerban Matei; Toader Corneliu; Covache-Busuioc Răzvan-Adrian — 2026
Score: 4/10 | Pathways: cGAS-STING, clinical-phenotype

ZBP1 senses oxidized mtDNA and self nucleic acids to trigger RIPK/MLKL inflammatory pathways in neuroinflammation, an innate-immune sensing mechanism parallel to but distinct from SAMHD1/cGAS-STING axis with only indirect relevance to the AuDHD/ME-CFS neuroinflammatory phenotype.
DOI: 10.3390/ijms27167478

Pathway Coverage This Week

  • cGAS-STING: 6 papers
  • treatment-target: 5 papers
  • ISG15-mitophagy: 3 papers
  • clinical-phenotype: 3 papers
  • NF-kB-NLRP3-priming: 2 papers
  • NLRP3: 1 papers
  • mito-ROS-NF-kB: 1 papers
  • mTOR-lysosomal: 1 papers
  • POLG-mtDNA: 1 papers
  • JAK-STAT: 1 papers
  • poliosis-neural-crest: 1 papers

SAMHD1 Research Digest — 2026-08-30

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 22 papers evaluated | 3 high-relevance (≥7) | 7 medium (5–6) | 12 low (3–4) | 0 scored <3

⚠️ Partial run: preprint returned no papers (likely rate-limited). Coverage this week is incomplete; the missed papers are not marked seen and will be picked up on the next run.

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Iterative genetic testing identifies SAMHD1 deficiency caused by a homozygous balanced translocation. (from Clinical genetics/genomics (structural variant diagnostics))
Baker Paul J; Zhang Yaoyuan; Bishop Imogen; Cleveland Madeline L; McAllan Alexan — Journal of human immunity 2026
Score: 9/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, dNTPase, clinical-phenotype

Directly demonstrates SAMHD1 loss-of-function via a novel structural variant (balanced translocation) causing type I interferon signature and familial chilblain lupus, reinforcing the core SAMHD1-interferonopathy mechanism relevant to the A565T haploinsufficiency model.
DOI: 10.70962/jhi.20260044

Mitophagy mitigates mitochondrial DNA-induced activation of cGAS-STING in autoimmune thyroiditis (from Endocrinology (autoimmune thyroiditis))
Xiao-Chen Xie; Yang Guo; Ran Guo; Yongze Li; Shan-Shan Wang — Nature Communications 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, NF-kB-IKK, treatment-target, clinical-phenotype

Demonstrates that mitophagy failure (PINK1/Parkin/TAX1BP1 axis, mechanistically parallel to ISG15-mediated mitophagy block in the RED stream) causes mtDNA leakage and cGAS-STING-driven autoimmune inflammation, directly reinforcing the BLUE/RED loop mechanism and validating STING inhibition (C176) as a therapeutic strategy relevant to the SAMHD1 interferonopathy model.
DOI: 10.1038/s41467-026-76047-9

APOE4-AGE axis is linked to mtDNA release and cGAS-STING mediated neuroinflammation in the aging brain. (from Neurodegeneration/Alzheimer's disease research)
Akhter Firoz; Akhter Asma; Zhou Jasmine; Xi Michelle; Zhu Donghui — Free radical biology & medicine 2026
Score: 7/10 | Pathways: cGAS-STING, mito-ROS-NF-kB, clinical-phenotype

Demonstrates mtDNA release triggering cGAS-STING-TBK1-IRF3-driven type I interferon and neuroinflammation via mitochondrial dysfunction, directly paralleling the BLUE loop mechanism (VDAC1/mtDNA/cGAS/STING/IFN-I) central to the SAMHD1 syndrome, though in an APOE4/AGE-RAGE rather than SAMHD1 context.
DOI: 10.1016/j.freeradbiomed.2026.08.054

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

Mitochondrial immunometabolism in sepsis: bridging immune cell dysfunction and organ failure (from Critical care/sepsis immunometabolism)
Xingzhan Zhang; Ling Zhao; Wei Fu; Lili Pan; Huanhuan Wu — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target

Reviews mitochondrial mtDNA/mtROS-driven cGAS-STING and NLRP3 activation and its crosstalk with NF-kB in immune cells, mechanistically overlapping with the BLUE/PURPLE/GOLD loops in the SAMHD1 model even though sepsis rather than SAMHD1 haploinsufficiency is the trigger.
DOI: 10.3389/fimmu.2026.1921226

Interferon Regulatory Factors as Potential Therapeutic Targets in Cardiovascular Disease: Focusing on Vascular Inflammation (from Cardiology/vascular biology)
Chen-Xi Bai; Wei-Xu Liu; Yu-Bo Wang; Hui-Xia Zhu; Xing Fan — International Journal of Molecular Sciences 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, NF-kB-IKK, treatment-target

Reviews IRF1/3/5/7 pro-inflammatory signaling via cGAS-STING/NLRP3/NF-kB/JAK-STAT in vascular disease, mechanistically parallel to the IFN-I/NLRP3 axis in SAMHD1 A565T interferonopathy but without direct SAMHD1 or mitochondrial dNTP linkage, and offers cardiovascular relevance given the family's cardiac/vascular phenotype risk.
DOI: 10.3390/ijms27177647

p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages. (from virology/pharmacology (HIV restriction and nutraceutical NRF2 signaling))
Marcelino Bianka Nicolle Pena; Girard Kiersten; Letourneau Lauren; Lewin Andrew; — Biomolecules 2026
Score: 6/10 | Pathways: dNTPase, treatment-target, other

Demonstrates regulation of SAMHD1 phosphorylation (T592) via p21/CDK in macrophages and its role in antiviral restriction, relevant to SAMHD1 functional regulation though not the A565T dNTPase catalytic mechanism directly.
DOI: 10.3390/biom16081213

Investigating the Role of Type I Interferon Signaling on Muscle Disease Using Mouse Models. (from Rheumatology/Muscle disease (myositis))
Spathis Rita; Narvesen Sabrina; Robles Kuriplach Deeva; Huang Karen; Sundar Teja — Arthritis & rheumatology (Hoboken, N.J.) 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype

Demonstrates JAK inhibitor (tofacitinib) suppression of type I IFN signature and improved survival in murine myositis models driven by IFN-beta overexpression, directly supporting JAK-STAT as a therapeutic target relevant to the SAMHD1 interferonopathy mechanism though not SAMHD1-specific.
DOI: 10.1002/art.70096

Development of mitochondrial mutator pigs exhibiting increased mitochondrial DNA mutations and premature aging via prime editing. (from Comparative/translational aging biology using large-animal (porcine) prime-editing models)
Chen Fangbing; Liang Yanhui; Zheng Wei; Yao Aobo; Wang Ning — Science advances 2026
Score: 5/10 | Pathways: POLG-mtDNA, prime-editing, gene-therapy-delivery

Demonstrates POLG proofreading-deficiency-driven mtDNA mutation accumulation and premature aging using prime editing in a large animal model, directly relevant to the PURPLE-stream POLG stalling node and to prime-editing technology tracked for future SAMHD1 correction, though not immune-cell or SAMHD1-specific.
DOI: 10.1126/sciadv.adu0632

Alcohol intake reprograms hepatic immune-metabolic circuits to exacerbate murine atherosclerosis and human cardiovascular risk. (from Hepatology/Cardiology)
Hoebinger Constanze; Semmler Georg; Petrenko Oleksandr; Rajcic Dragana; Hoffelne — JHEP reports : innovation in hepatology 2026
Score: 5/10 | Pathways: urate-NLRP3, NLRP3, clinical-phenotype

Demonstrates hyperuricemia-driven hepatic NLRP3 upregulation and inflammasome activation linked to dyslipidemia and cardiovascular risk, paralleling the GOLD pathway (dGTP→purine catabolism→uric acid→NLRP3) in the SAMHD1 model though not SAMHD1-specific.
DOI: 10.1016/j.jhepr.2026.101932

Understanding cardiovascular aging as a disorder of mitochondrial network (from Cardiology/cardiovascular aging)
Taslima Akter Shila; Dhrubo Ahmad; Jianli Zhao; Huilan Tan; Bo Wang — The journal of cardiovascular aging 2026
Score: 5/10 | Pathways: cGAS-STING, mito-ROS-NF-kB, clinical-phenotype

This review discusses mitochondrial DNA/vesicle release activating cGAS-STING and driving sterile inflammation in cardiovascular aging, which parallels the SAMHD1-driven mitochondrial-interferon mechanism but lacks direct SAMHD1 or NLRP3/inflammasome linkage and focuses on aging rather than the specific disease pathway.
DOI: 10.20517/jca.2026.07

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

From mechanical adaptation to innate immune reprogramming in osteoarthritis: a load-immunity framework (from Orthopedics/Rheumatology (mechanobiology of osteoarthritis))
Shiguo Zuo; Lijun He; Z. Hou; Quanliang Tian; Yilong Yang — Frontiers in Immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB

Discusses cGAS-STING and NLRP3 mitochondrial danger-signal pathways shared with the SAMHD1 mechanism but in an osteoarthritis mechanical-loading context unrelated to SAMHD1 dysfunction or the family phenotype spectrum.
DOI: 10.3389/fimmu.2026.1931112

Post-translational control of MAVS signaling: linking mitochondrial antiviral immunity to metabolic and cellular stress contexts (from Mitochondrial biochemistry/virology (PTM signaling biology))
Nao Morimoto; Tomohiko Okazaki — Frontiers in Physiology 2026
Score: 4/10 | Pathways: cGAS-STING, VDAC1, other

This paper details PTM regulation of MAVS, a mitochondrial RLR adaptor producing type I IFN, offering a conceptually parallel but mechanistically distinct pathway to the SAMHD1-VDAC1-cGAS-STING axis without direct SAMHD1 or NLRP3/ISG15 involvement.
DOI: 10.3389/fphys.2026.1907325

Advances in prime editing: Molecular innovations, Large-fragment engineering, and AI-driven design. (from genome engineering/synthetic biology)
Muhammad Waqar; Cao Xi; Umar Aziz; Nauman Khan; Jiao Ziao — Biodesign research 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General review of prime editing technology advances with no immune/myeloid-specific application or SAMHD1 correction focus, offering only background relevance to future gene therapy translation.
DOI: 10.1016/j.bidere.2026.100104

The Role of Skeletal Muscle Mitochondria in NLRP3 Inflammasome Signaling. (from exercise physiology/skeletal muscle biology)
Sangha Jada; Hood David A — Biomolecules 2026
Score: 4/10 | Pathways: NLRP3, mito-ROS-NF-kB

Reviews mitochondrial DAMP-driven NLRP3 activation and exercise mitigation in skeletal muscle, relevant to the mitochondrial-inflammasome mechanism but lacks SAMHD1, interferon, or clinical-phenotype connections central to this disease profile.
DOI: 10.3390/biom16081218

Glyphosate induces intestinal inflammatory injury associated with mitochondrial-lysosomal dysfunction, cGAS-STING activation, and pyroptosis-related responses in common carp (Cyprinus carpio L.). (from aquatic toxicology/veterinary environmental science)
Zhang Shuyue; Ji Xiaofeng; Zhong Haoyu; Wang Zehui; Li Xiaohui — Fish & shellfish immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB

This fish toxicology study demonstrates mtDNA release-cGAS-STING-NLRP3-pyroptosis signaling analogous to Loop A/B mechanisms in the SAMHD1 model, but is a non-mammalian xenobiotic toxicity paper without direct genetic or clinical relevance to SAMHD1 haploinsufficiency.
DOI: 10.1016/j.fsi.2026.111682

Non-invasive Ultra-early in Utero Detection and Precision CRISPR-mediated Correction of Monogenic Embryonic Mutations: A Critical Appraisal of a Hypothetical Therapeutic Framework (from Prenatal diagnostics / gene therapy delivery)
S. Bittmann; E. Luchter; E. Moschüring-Alieva — Asian Journal of Medicine and Health 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery, pregnancy-fetal

This is a general critical review of in utero cfDNA detection and CRISPR/prime-editing correction for monogenic disease, not specific to SAMHD1 or its core inflammatory pathways, but tangentially relevant as background for future gene-correction strategies applicable to a heterozygous missense variant like A565T.
DOI: 10.9734/ajmah/2026/v24i91427

From immune dysregulation to renal injury: mechanistic insights and translational opportunities in immune-mediated nephropathies (from Nephrology/Rheumatology)
Xiaoming Wang — Frontiers in Cell and Developmental Biology 2026
Score: 3/10 | Pathways: NLRP3, cGAS-STING, JAK-STAT, NF-kB-IKK

This is a general nephrology review of immune-mediated kidney diseases touching on shared innate-immune pathways (NLRP3, cGAS-STING, NF-kB, JAK-STAT) that overlap thematically with the SAMHD1 interferon-mitochondrial mechanism but has no direct SAMHD1, mitochondrial dNTP, or ME/CFS/family phenotype connection.
DOI: 10.3389/fcell.2026.1878787

A PepFect14 analog improves non-viral CRISPR delivery in primary human cells to facilitate genome editing and repair. (from Dermatology/gene therapy bioengineering)
A. du Rand; Courtney Masterson; Daniel J Verdon; Andrew Siow; E. Loef — Bioengineering & translational medicine 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper describes a non-viral CRISPR delivery peptide for skin cell genome editing in epidermolysis bullosa, which is a gene-editing delivery advance but not targeted at myeloid/immune cells or SAMHD1 correction and thus only tangentially related.
DOI: 10.1002/btm2.70172

Delivering the blueprint: Advances and challenges in mRNA therapeutics for the respiratory system (from pulmonology/pharmaceutics)
Fangru Jia; Linlin Ma; Yanan Li — International Journal of Pharmaceutics: X 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This review covers mRNA-LNP delivery to lung tissue generally, with only tangential relevance to SAMHD1 gene therapy since it doesn't address myeloid/HSC editing or immune cell delivery specific to the disease model.
DOI: 10.1016/j.ijpx.2026.100634

Neurotensin receptor agonist PD149163 modulates LPS-induced sub-acute gut inflammation by inhibiting TLR4/NF-κB/NLRP3 inflammasome pathway: In vivo, in silico and network pharmacology analyses. (from Gastroenterology/pharmacology)
Singh Priya; Mohanty Banalata — International immunopharmacology 2026
Score: 3/10 | Pathways: NLRP3, NF-kB-IKK

This paper studies TLR4/NF-κB/NLRP3 inhibition by a neurotensin receptor agonist in LPS-induced gut inflammation in mice, sharing pathway components with the SAMHD1 model but with no connection to SAMHD1, interferonopathy, or mitochondrial dNTP mechanisms.
DOI: 10.1016/j.intimp.2026.117321

Pain and Analgesic Doses Versus Free Interleukin 18 (IL-18F) Blood Levels Following Surgery: A Prospective Randomized Study of Patients With Minilaparotomy Cholecystectomy Versus Laparoscopic Cholecystectomy. (from Surgery/pain medicine)
Eskelinen Matti; Kuosmanen Viivi; Selander Tuomas; Kaarniranta Kai; Saimanen Iin — In vivo (Athens, Greece) 2026
Score: 3/10 | Pathways: NLRP3, clinical-phenotype

This paper studies IL-18/IL-18BP as postoperative pain biomarkers after cholecystectomy, touching the NLRP3-IL-18 axis and the family's cholecystectomy clustering phenotype but without any SAMHD1, interferon, or mitochondrial mechanism linkage.
DOI: 10.21873/invivo.14435

Generation of two homozygous iPSC lines carrying variants of uncertain significance in LMNA associated with cardiomyopathy. (from Cardiology/stem cell genetics)
Liu Lu; Wu David; Manhas Amit; Noishiki Chikage; Tripathi Dipti — Stem cell research 2026
Score: 3/10 | Pathways: prime-editing

This paper demonstrates prime editing to generate LMNA VUS iPSC lines for cardiomyopathy research, technically relevant to gene correction methodology but unrelated to SAMHD1 or its associated pathways.
DOI: 10.1016/j.scr.2026.104086

Pathway Coverage This Week

  • cGAS-STING: 10 papers
  • NLRP3: 9 papers
  • clinical-phenotype: 7 papers
  • mito-ROS-NF-kB: 6 papers
  • treatment-target: 5 papers
  • gene-therapy-delivery: 5 papers
  • JAK-STAT: 4 papers
  • NF-kB-IKK: 4 papers
  • prime-editing: 4 papers
  • dNTPase: 2 papers
  • other: 2 papers
  • AGS-spectrum: 1 papers
  • ISG15-mitophagy: 1 papers
  • POLG-mtDNA: 1 papers
  • urate-NLRP3: 1 papers
  • VDAC1: 1 papers
  • pregnancy-fetal: 1 papers

SAMHD1 Research Digest — 2026-08-23

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 16 papers evaluated | 1 high-relevance (≥7) | 6 medium (5–6) | 9 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Targeting mPTP with NIM811 Alleviates Pancreatic Injury and Inflammatory Response in Severe Acute Pancreatitis (from Gastroenterology/Critical Care (acute pancreatitis))
Feng Dan; Zhang Jia-Rui; Bai Xue; Chen Xia — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, treatment-target, other

Demonstrates mPTP/VDAC-adjacent mitochondrial membrane permeability leading to mtDNA release and cGAS-STING-driven inflammatory cytokine production (IL-1β, IL-6, TNF-α) in a mitochondrial damage model, directly paralleling the BLUE loop mechanism (mtDNA escape → cGAS/STING → IFN-inflammatory output) though in a distinct disease context (pancreatitis) without SAMHD1 involvement.
DOI: 10.21203/rs.3.rs-10616969/v1

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

The dual role of the cGAS-STING signaling pathway in kidney diseases: from acute injury to chronic fibrosis – molecular mechanisms and precision therapeutic strategies (from Nephrology)
Guangdong Qi; Fei Xue; Hualin Sun; Xinlei Yao; Qingyuan Liu — Frontiers in Pharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Reviews cGAS-STING mechanisms (mtDNA leakage, TBK1-IRF3/NF-kB, inflammation-fibrosis) and inhibitor strategies directly relevant to the BLUE loop pathway, though applied to renal disease rather than SAMHD1 context.
DOI: 10.3389/fphar.2026.1882994

Quercetin induces molecular hallmarks of immunogenic cell death and cGAS-STING pathway activation via mitochondrial DNA release in hepatocellular carcinoma cells. (from Oncology/pharmacology)
Lin Tong; Chen Yifan; Huang Zhengrong — Naunyn-Schmiedeberg's archives of pharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

Demonstrates mtDNA release triggering cGAS-STING-TBK1-IRF3/p65 activation, directly modeling the core Loop A/NF-kB crosstalk mechanism though in an oncology drug-induction context rather than SAMHD1 dysfunction.
DOI: 10.1007/s00210-026-05815-7

Expanding the therapeutic landscape of Still's disease: the emerging role of JAK inhibitors. (from Rheumatology)
Ruscitti Piero; Ursini Francesco; Giacomelli Roberto; Cantarini Luca; Caso Franc — Expert opinion on pharmacotherapy 2026
Score: 6/10 | Pathways: JAK-STAT, NLRP3, treatment-target, clinical-phenotype

Reviews JAK inhibitors modulating IL-1/IL-6/IFN-γ and inflammasome-dependent pathways in Still's disease, directly relevant to the JAK-STAT and NLRP3 nodes and to JAKi therapeutic strategies applicable to the interferon-mitochondrial syndrome, though not SAMHD1-specific.
DOI: 10.1080/14656566.2026.2723582

Mitochondrial DNA in necrosis-like cell death in failing hearts: evidence and mechanisms fostering damage. (from cardiology)
Marciníková Andrea; Jarabicová Izabela; Horváth Csaba; Adameova Adriana — American journal of physiology. Cell physiology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target, other

This cardiology-focused review details mtDNA release triggering cGAS-STING and NLRP3/AIM2 inflammasome pathways driving necroptosis/pyroptosis in heart failure, mechanistically overlapping with the BLUE loop (VDAC1/mtDNA/cGAS-STING) and NLRP3 activation streams central to the SAMHD1 disease model, though it does not address SAMHD1 or dNTPase biology directly.
DOI: 10.1152/ajpcell.00266.2026

The Role of Skeletal Muscle Mitochondria in NRLRP3 Inflammasome Signaling (from exercise physiology/skeletal muscle biology)
Jada Sangha; David A. Hood — Biomolecules 2026
Score: 5/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

Reviews NLRP3 inflammasome activation via mitochondrial DAMPs (ROS, oxidized mtDNA) in skeletal muscle, mechanistically overlapping with the disease's mitochondrial-inflammasome axis but without SAMHD1, cGAS-STING, or IFN-I context, and exercise/myokine focus is only indirectly relevant to ME/CFS fatigue phenotype.
DOI: 10.3390/biom16081218

Systemic effects of gout flares beyond the joints. (from Rheumatology/Cardiology)
Cipolletta Edoardo; Mamas Mamas A; Abhishek Abhishek — Current opinion in rheumatology 2026
Score: 5/10 | Pathways: urate-NLRP3, NLRP3, treatment-target

Discusses gout flare-driven NLRP3/IL-1β activation and cardiovascular sequelae, directly relevant to the GOLD stream (dGTP→uric acid→MSU crystals→NLRP3) and family gout/uric acid phenotype but not tied to SAMHD1 or interferon mechanisms.
DOI: 10.1097/BOR.0000000000001183

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Atomic-Level Strain-Engineered Piezoelectric Nanosheets for cGAS-STING Activation. (from materials science/nanomedicine oncology)
Yang Lu; Zang Pengyu; Zhang Rui; Yang Meiqi; Yu Chenghao — 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target

This paper describes a nanomaterial-based tumor immunotherapy that activates cGAS-STING via mtDNA release, sharing a mechanistic node with the disease's BLUE pathway but in an unrelated oncologic engineering context with no SAMHD1 or interferonopathy relevance.
DOI: 10.1002/anie.5643285

Mitochondrial metabolic remodelling during bacterial infection: Molecular mechanisms, cellular consequences, and therapeutic opportunities. (from Microbiology/Infectious Disease)
Kowalik Agnieszka; Paszenda Patrycja; Frątczak Agnieszka; Piwowar Adrian; Obryck — Tissue & cell 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, mito-ROS-NF-kB

This review covers mitochondrial-immune crosstalk mechanisms (cGAS-STING, NLRP3, ROS-NF-kB, mitochondrial fragmentation) overlapping with the disease's core pathways, but is focused on bacterial infection biology rather than SAMHD1 dysfunction or interferonopathy syndromes.
DOI: 10.1016/j.tice.2026.103873

Gut microbiota–mitochondria–barrier–multiorgan axis: a network-based hypothesis for systemic injury (from Gastroenterology/critical care medicine)
Yachao Li; Huaijue Qiu; Xia Gao; Yanling Zhang; Qin Xia — Frontiers in Immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, other

This paper discusses cGAS-STING and NLRP3 activation via mitochondrial DAMPs in a gut-microbiota-critical illness context, sharing core mechanistic pathways but lacking any SAMHD1, interferonopathy, or family phenotype connection.
DOI: 10.3389/fimmu.2026.1885379

Genome Editing in Primary Mammalian Cells via Electroporation of Editor RNA. (from molecular biology/gene editing methodology)
Maria Viskadourou; J. Workman; Emma V Burke; D. M. Eckley; Johannes Dohr — Journal of visualized experiments : JoVE 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General methods paper on mRNA-based genome editing delivery in primary cells, relevant as generic platform technology for future SAMHD1 correction but not disease-specific or immune/myeloid-focused.
DOI: 10.3791/71449

FGFR4 suppresses antitumor immunity and cuproptosis by disrupting CYLD-mediated stabilization of STING and FDX1. (from Oncology (tumor immunology/cancer therapeutics))
Zhong Hongguang; Huang Ruixuan; Deng Wenyuan; Ruan Ruiwen; Dai Xiaofeng — 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target, other

This paper involves cGAS-STING pathway regulation via CYLD/FDX1/cuproptosis in cancer immunotherapy, but is oncology-focused with no connection to SAMHD1, dNTP metabolism, or interferonopathy mechanisms central to this disease profile.
DOI: 10.1016/j.canlet.2026.218790

Epithelial interferon-stimulated gene programs modulate chemotherapy sensitivity in colorectal cancer via EPSTI1. (from Oncology)
Erkan Erdogan Pekcan; Hämäläinen Emmi; Kolikova Julia; Nikupaavola Tiia; Sajnani — Oncogene 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

Discusses JAK-STAT/ISG program and ruxolitinib in a colorectal cancer oncology context, tangentially touching interferon signaling but without SAMHD1, mitochondrial, or innate immune inflammasome mechanisms central to the disease profile.
DOI: 10.1038/s41388-026-03957-9

Dysfunction of the Neurovascular Unit in Diabetic Retinopathy: Advances from Molecular Mechanisms to Targeted Interventions. (from Ophthalmology)
Zhao Chunning; Qin Leilei; Zhang Jing; Wang Xiu — Stem cell reviews and reports 2026
Score: 3/10 | Pathways: NLRP3, other

This is a diabetic retinopathy review touching on NLRP3/mitochondrial dysfunction in a generic ophthalmology context, without any SAMHD1, interferon, or family-phenotype linkage.
DOI: 10.1007/s12015-026-11213-6

Alopecia Areata: Current and Emerging Therapies. (from Dermatology)
Domingues João; King Brett; Torres Tiago — Drugs 2026
Score: 3/10 | Pathways: JAK-STAT, treatment-target

Reviews JAK inhibitors (baricitinib) for alopecia areata, relevant as a JAK-STAT therapeutic class overlapping with interferonopathy management but not directly tied to SAMHD1 mechanism or family phenotypes.
DOI: 10.1007/s40265-026-02371-5

Integrated Multi-omics Reveals CDKN1A Suppression and Metabolic Regulation as Key Mechanisms of Huangqi Guizhi Wuwu Decoction Against Doxorubicin-Induced Cardiotoxicity. (from Cardio-oncology/pharmacology (traditional Chinese medicine))
Hou Qian; Yu Xinyue; Wu Ke; Chen Siling; Mao Xin — Cardiovascular toxicology 2026
Score: 3/10 | Pathways: ISG15-mitophagy, other

This paper on a Chinese herbal decoction mitigating doxorubicin cardiotoxicity incidentally identifies Irf7/Isg15 and apoptosis genes (Bax, Cdkn1a) but has no mechanistic connection to SAMHD1, interferonopathy, or the core inflammasome/mitochondrial pathways central to this disease profile.
DOI: 10.1007/s12012-026-10168-x

Pathway Coverage This Week

  • treatment-target: 11 papers
  • cGAS-STING: 8 papers
  • NLRP3: 7 papers
  • other: 6 papers
  • NF-kB-IKK: 3 papers
  • JAK-STAT: 3 papers
  • mito-ROS-NF-kB: 3 papers
  • VDAC1: 1 papers
  • clinical-phenotype: 1 papers
  • urate-NLRP3: 1 papers
  • prime-editing: 1 papers
  • gene-therapy-delivery: 1 papers
  • ISG15-mitophagy: 1 papers

Emerging microbiome–mitochondria crosstalk in host defense and infectious diseases: mechanistic insights into NLRP3 inflammasome activation and mtDNA-mediated immunomodulation

The finding

This review synthesizes recent evidence that gut microbiota metabolites—short-chain fatty acids, trimethylamine, and indole derivatives—directly modulate mitochondrial function and reactive oxygen species (ROS) production, which in turn gates NLRP3 inflammasome activation. The authors also consolidate findings that dysbiosis promotes mitochondrial stress and mtDNA release, with mtDNA acting as a damage-associated molecular pattern that can engage both cGAS-STING and NLRP3 signaling, linking gut microbial shifts to systemic inflammation across colitis, neurodegeneration, and sepsis.

Where it fits

This review speaks directly to Loop B (mitochondrial/NLRP3) and provides a critical checkpoint insight relevant to SAMHD1 A565T. The paper's central claim—that mitochondrial ROS and mtDNA fragmentation are upstream licensing events for NLRP3—mirrors the model's proposed mechanism whereby POLG replisome stress generates oxidized mtDNA (8-OHdG) that primes NLRP3 rather than cGAS. The review's emphasis on PINK1/Parkin-mediated mitophagy as a brake on this pathway is directly relevant: in the SAMHD1 model, ISG15 ISGylates MFN1/2 and BECN1 to block mitophagy, creating a self-sustaining loop. The review also reinforces the dual-sensor logic—mtDNA can hit both cGAS-STING and NLRP3 via distinct routes—which is the model's central testable claim. Finally, the microbiome–mitochondria axis suggests an environmental modifier: gut-derived metabolites could tune the threshold for NLRP3 licensing in SAMHD1 carriers, potentially explaining variable penetrance.

Caveats

  • This is a review, not primary data; the mechanistic links are synthesized from disparate studies, often in different cell types or disease models.
  • The microbiome–mitochondria–NLRP3 connections are largely demonstrated in non-SAMHD1 contexts (colitis, sepsis); extrapolation to SAMHD1 A565T is inferred, not tested.
  • The review does not address heterozygous vs. homozygous loss-of-function, nor does it quantify how much mitochondrial stress is needed to cross the NLRP3 activation threshold.

What to watch

Does modulating the gut microbiome—via probiotics or metabolite supplementation—alter NLRP3-dependent IL-18/IL-1β output in SAMHD1 models? If so, the microbiome becomes a druggable upstream node for Loop B, potentially complementing JAK inhibition that targets Loop A.

Source: Emerging microbiome–mitochondria crosstalk in host defense and infectious diseases: mechanistic insights into NLRP3 inflammasome activation and mtDNA-mediated immunomodulation — Frontiers in Cellular and Infection Microbiology 2026.

HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway

The finding

This paper shows that the HTLV-1 Tax protein hijacks the PINK1–Parkin mitophagy pathway to clear damaged mitochondria and suppress cGAS–STING activation. Tax induces mitochondrial ROS and membrane-potential disruption, then recruits the autophagy receptors CALCOCO2/NDP52 and SQSTM1/p62 to drive mitophagic clearance. Critically, Tax requires PRKN to limit cGAS-STING1 activation and type I interferon induction — a viral immune-evasion strategy that also sustains viral gene expression and cell survival.

Where it fits

This speaks directly to Loop A (IFN-I/JAK-STAT) and the mitochondrial quality-control node that the SAMHD1 A565T model predicts is corrupted. In the SAMHD1 model, ISG15 ISGylates MFN1/2 and BECN1, blocking mitophagy so damaged mitochondria persist and keep leaking mtDNA to cGAS-STING. This paper provides the mechanistic counterexample: when PINK1-Parkin mitophagy works, it clears damaged mitochondria and prevents cGAS-STING activation. That is exactly the clearance step the SAMHD1 model predicts is disabled — and it confirms that mitophagy is a genuine checkpoint for tonic IFN-I, not just a downstream consequence of mitochondrial stress.

The paper also reinforces the model's claim that mtDNA release is the key ligand for cGAS: Tax's suppression of IFN depends on removing the mitochondria that would otherwise release mtDNA, not on directly inhibiting cGAS itself.

Caveats

  • This is a viral system (HTLV-1 Tax), not a SAMHD1 model — the relevance is mechanistic analogy, not direct demonstration in A565T cells.
  • The experiments use overexpression and viral-transformed cell lines, not primary cells from SAMHD1 patients; the mitophagy-cGAS link is established here, but the specific failure mode in A565T remains inferred.
  • The paper shows Tax requires PRKN to suppress cGAS-STING, but does not address whether partial loss of mitophagy (as predicted in SAMHD1 A565T) produces a graded, smouldering IFN response versus an all-or-nothing switch.

What to watch

Does restoring PINK1-Parkin activity in SAMHD1 A565T cells — for example, by blocking ISG15-mediated inhibition of mitophagy — phenocopy Tax's suppression of cGAS-STING? That would be the direct test of whether the model's Loop A is truly self-sustaining via mitophagy blockade.

Source: HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway — 2026.

SAMHD1 Research Digest — 2026-08-16

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 29 papers evaluated | 2 high-relevance (≥7) | 14 medium (5–6) | 13 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Simulated Microgravity Induced Mesenchymal Stem Cell Senescence via the Activation of Cytosolic mtDNA-cGAS-STING Axis. (from Aerospace/regenerative medicine (stem cell biology under microgravity))
Huang Lei; Huang Rui; Lv Wenjun; Li Zimeng; Tu Yun — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, treatment-target

This paper directly demonstrates the BAK/BAX-VDAC-mediated mtDNA leakage → cGAS-STING activation axis (BLUE stream) driving cellular senescence, mechanistically paralleling the core interferon-mitochondrial pathway implicated in the SAMHD1 A565T syndrome, with STING inhibition (C176) shown as a viable therapeutic strategy.
DOI: 10.1002/jcp.70220

Taulipro rescues mitochondrial dysfunction and inhibits cGAS–STING neuroinflammation in Aβ-driven Alzheimer's disease models (from Neurology/Neurodegeneration (Alzheimer's disease))
Tian Mao; Zhu Xiuping; Lei Zhifeng; Lu Yongheng; Mo Lin — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, NF-kB-IKK, treatment-target

This paper demonstrates mtDNA leakage-driven cGAS-STING-TBK1-IRF3-NFκB neuroinflammation as an upstream pathogenic mechanism directly analogous to the BLUE/RED loops in the SAMHD1 interferon-mitochondrial syndrome, with a novel therapeutic (Taulipro) targeting the mtDNA leakage step relevant to future treatment strategies.
DOI: 10.21203/rs.3.rs-10416296/v1

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

Honokiol targets cyclophilin D and blocks mitochondrial DNA release to inhibit microglial NLRP3 inflammasome activation and alleviate neurodegeneration in Parkinson's disease models. (from Neurology/neurodegeneration (Parkinson's disease) and natural product pharmacology)
Gan Qinglin; Xian Yingtong; Zhou Ting; Fu Xiaolong; Gou Shiyi — Chemico-biological interactions 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

This paper demonstrates mtDNA release triggering NLRP3 inflammasome activation via mitochondrial permeability transition (CypD), mechanistically parallel to the VDAC1/mtDNA-NLRP3 axis central to the SAMHD1 syndrome, and offers a small-molecule therapeutic (honokiol) strategy relevant to inflammasome modulation.
DOI: 10.1016/j.cbi.2026.112305

Hepatocyte hnRNPK preserves mitochondrial integrity to restrain liver injury and fibrosis. (from Hepatology)
Peng Qian; Wang Sujuan; Zhang Yufeng; Luo Yangjun; Lan Beiwu — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype

This paper demonstrates mitochondrial fragmentation (via OPA1 splicing dysregulation) leading to cytosolic mtDNA release and cGAS-STING activation driving fibrotic inflammation, mechanistically paralleling the BLUE loop (VDAC1/mtDNA-cGAS-STING) in the SAMHD1 profile despite a different upstream trigger and hepatic rather than systemic context.
DOI: 10.1097/hep.0000000000001836

TANK-binding kinase 1 (TBK1): unexpected cell type-specific immune regulation beyond antiviral type I interferon signaling. (from virology/vaccinology)
Almeida Mariana S; Bezbradica Jelena S; Coban Cevayir — Current opinion in virology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

TBK1 is the key non-canonical IKK kinase (IKKe/TBK1 partner) linking cGAS-STING/IRF3 to both IFN-I and NF-kB signaling, and this review's discussion of cell-type-specific TBK1 functions and pharmacological inhibition is directly relevant to the STING-IRF3-NFkB crosstalk axis and potential therapeutic targeting in the interferonopathy mechanism.
DOI: 10.1016/j.coviro.2026.101545

Structural and single-molecule insights into the core human mitochondrial DNA replisome. (from structural biology/biochemistry)
Plaza-G A Ismael; Miguez-Amil Samuel; Hayes Allison M; Ciesielski Grzegorz L; Fe — The Biochemical journal 2026
Score: 6/10 | Pathways: POLG-mtDNA, mito-dNTP-transport

Detailed structural insight into the Polγ/Twinkle/mtSSB replisome is directly relevant to the POLG-stalling and mtDNA replication stress steps implicated in the PURPLE pathway of this syndrome's mechanism.
DOI: 10.1042/BCJ20260373

Emerging microbiome–mitochondria crosstalk in host defense and infectious diseases: mechanistic insights into NLRP3 inflammasome activation and mtDNA-mediated immunomodulation (from Microbiology/gastroenterology (gut microbiome-mitochondria crosstalk))
Xinxing Lu; Wenbin Sun; Daowei Zhang; Bin Hou; Huiyu Tai — Frontiers in Cellular and Infection Microbiology 2026
Score: 6/10 | Pathways: NLRP3, cGAS-STING, ISG15-mitophagy, mito-ROS-NF-kB, other

Reviews mtDNA-driven cGAS-STING/NLRP3 activation and PINK1/Parkin mitophagy as general mechanisms overlapping core disease pathways, though framed via gut microbiome rather than SAMHD1-specific dysregulation.
DOI: 10.3389/fcimb.2026.1866924

cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders. (from Neurology/Neuroimmunology)
Rahim Abdul; Zubair Shaik Mahammad; Ahamed Mustak; Das Soumi; Patel Royal — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype

This review details cGAS-STING/mtDNA-driven neuroinflammation (Loop A) and its therapeutic targeting, relevant to the AuDHD/neurological phenotype in the SAMHD1 family though not SAMHD1-specific.
DOI: 10.1007/s11481-026-10307-9

Subacute ruminal acidosis induces colonic inflammation and barrier damage via cGAS-STING pathway in Hu sheep fed a high-grain diet. (from Veterinary gastroenterology/animal science)
Meng Meijuan; Shi Xiaoli; Tu Yuanlu; Bai Yunfeng; Chang Guangjun — 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

This paper demonstrates mtDNA release triggering cGAS-STING/NF-κB pathway activation and downstream inflammation, mechanistically paralleling the BLUE loop (VDAC1/mtDNA/cGAS-STING) in the SAMHD1 syndrome model despite being an unrelated ruminant/agricultural species and disease context.
DOI: 10.1016/j.jnutbio.2026.110483

Vilazodone inhibits NLRP3 inflammasome assembly by targeting the NACHT domain and alleviates inflammatory disease. (from psychiatry/pharmacology (antidepressant drug repurposing))
Yang Xiangyu; Xiong Guifang; Yang Jie; Ma Xinyi; Qie Yuanzheng — International immunopharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Vilazodone directly inhibits NLRP3 inflammasome assembly (NACHT domain) and reduces MSU-induced inflammation, offering a potential repurposed therapeutic candidate relevant to the GOLD (uric acid/MSU-NLRP3) and general NLRP3 hyperactivation streams in this interferon-mitochondrial syndrome.
DOI: 10.1016/j.intimp.2026.117279

Novel natural inhibitor Rubimaillin targets NLRP3 R167/Y381 to ameliorate inflammatory and neurodegenerative diseases. (from Ethnopharmacology/natural product drug discovery)
Xiao Jing; Lan Zhen; Zhang Ran; Zhang Jie; Hu Zuobin — Journal of ethnopharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Identifies a natural NLRP3 inhibitor effective in gouty arthritis (MSU-induced, matching the GOLD pathway) and neurodegenerative models, offering a potential therapeutic candidate relevant to the NLRP3 hyperactivation axis in this syndrome.
DOI: 10.1016/j.jep.2026.122293

Lactate-Induced K370 Lactylation of STING Inhibits STING-TBK1 Signaling and Dampens Anti-Tumor Immunity. (from oncology/tumor immunometabolism)
Wu Yueyao; Wang Jingzhe; Chen Xu; Yang Yuntong; Wei Ping — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Reveals a novel post-translational (lactylation) regulatory checkpoint on STING-TBK1 signaling relevant to the BLUE loop's IFN-I output, though in an oncology/tumor immunity context rather than SAMHD1 interferonopathy.
DOI: 10.1002/advs.77209

Mechanistic machine learning for prediction of prime editing outcomes. (from computational genome editing / bioengineering)
Hsu Alvin; Chen Peter J; Li Angus H; Hemez Colin F; Gao Xin D — Nature biotechnology 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper presents a machine learning tool (OptiPrime) for optimizing prime editing efficiency, directly relevant to future gene correction strategies for missense mutations like SAMHD1 p.A565T, though it does not address SAMHD1 or the interferon-mitochondrial mechanism itself.
DOI: 10.1038/s41587-026-03261-7

Advances in paclitaxel-mediated remodeling of the gastric cancer immune microenvironment and sensitization to immune checkpoint inhibitors via cGAS-STING pathway activation triggered by mtDNA release: challenges and translational perspectives. (from Oncology (gastric cancer chemo-immunotherapy))
Wu Chu-Ying; Sun Zun-Long; Ye Kai — 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target, other

Describes mtDNA release activating cGAS-STING/type I interferon signaling, mechanistically overlapping with the BLUE loop, but in an oncology chemotherapy context unrelated to SAMHD1 or the family phenotype.
DOI: 10.1007/s11033-026-12570-8

Mitochondrial Dysfunction as a Driver of Meta-Inflammation in Aging: The Emerging Role of PDK4 in Bioenergetic Reprogramming and Inflammatory Amplification. (from metabolic/aging biology and endocrinology)
Chowdhury Md Riad; Jeong Gui-Hwa; Lee In-Kyu — 2026
Score: 5/10 | Pathways: NLRP3, cGAS-STING, NF-kB-IKK, mito-ROS-NF-kB, other

Reviews mitochondrial dysfunction driving NF-κB/NLRP3/cGAS-STING-mediated meta-inflammation via PDK4/pyruvate metabolism, an adjacent metabolic-inflammatory mechanism relevant to the family's mitochondrial-interferon axis but not SAMHD1-specific.
DOI: 10.3390/cells15151404

eVLP compound delivery breaks the prime editing efficiency ceiling. (from gene therapy/genome editing engineering)
Wang Margaret R; Sánchez-Rivera Francisco J — Cell genomics 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Describes an engineered virus-like particle (eVLP) repeated-dosing strategy (PRIME-VLP) that improves prime editing efficiency, relevant as a potential future delivery platform for correcting SAMHD1 point mutations but not disease-mechanism specific.
DOI: 10.1016/j.xgen.2026.101333

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Non-Invasive Scalp Tape-Strip RNA Sequencing Captures Disease Activity and Treatment-Response Signatures in Alopecia Areata. (from Dermatology)
Mochón-Jiménez Carmen; Gay-Mimbrera Jesús; Dávila-Flores Viviana; He Helen; Zhou — Allergy 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

Alopecia areata tape-strip transcriptomics highlights IFN/JAK-STAT and baricitinib response signatures, mechanistically adjacent to the interferonopathy axis but not connected to SAMHD1 or the family's core mitochondrial-inflammasome pathways.
DOI: 10.1111/all.70293

Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2 (from genomics/bioinformatics methodology)
Tingting Cong; Runda Xu; Xuancheng Chen; Junsong Yuan; Zuomiao Lin — Nature Communications 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This paper presents an off-target detection method for CRISPR editors relevant to future gene correction of SAMHD1 variants but has no direct disease mechanism or immune pathway content.
DOI: 10.1038/s41467-026-76778-9

Inflammatory kinase TBK1 suppresses homologous recombination DNA repair to sensitize tumors to chemotherapy. (from Oncology/DNA damage response)
Zhou Wei; Wang Xiangyu; Steigleder Susanne S; Xing Aowei; Yang Dan — Proceedings of the National Academy of Sciences of the United States of America 2026
Score: 4/10 | Pathways: NF-kB-IKK, other

TBK1 (IKKε/TBK1 axis) is a named kinase in the interferonopathy mechanism, but this paper focuses on its DNA-repair/chemotherapy role independent of cytokine or STING/IRF3 signaling, making it only tangentially relevant.
DOI: 10.1073/pnas.2533402123

Prime Editing Mediated Generation and Correction of the mdx5cv Mutation Restores Dystrophin Expression in Myoblasts (from Neuromuscular genetics / gene therapy)
A. Siddika; F. Husseiny; J. Rousseau; J. Tremblay — International Journal of Molecular Sciences 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

Demonstrates a generalizable prime editing correction workflow for a pathogenic point mutation restoring protein expression, methodologically relevant to future SAMHD1 A565T correction but unrelated disease (DMD) and non-immune cell type.
DOI: 10.3390/ijms27156927

In Vivo Base Editing for Neonatal Inborn Errors of Metabolism: Clinical Progress, N-of-1 Therapy, and the Ethics of Bespoke Genetic Medicine. (from Neonatology/Genetic Medicine Ethics)
Li Oscar Mingtian; Li Yijiang; Li Summer Xia Tian — Cureus 2026
Score: 4/10 | Pathways: gene-therapy-delivery, prime-editing

This paper reviews in vivo base editing for neonatal metabolic disorders using LNP delivery, relevant as a generalizable precedent for correcting a heterozygous missense variant like SAMHD1 A565T but not targeting immune/myeloid cells or the interferon-mitochondrial mechanism directly.
DOI: 10.7759/cureus.114354

From mechanical adaptation to innate immune reprogramming in osteoarthritis: a load-immunity framework (from Orthopedics/Rheumatology (mechanobiology of joint disease))
Shiguo Zuo; Lijun He; Z. Hou; Quanliang Tian; Yilong Yang — Frontiers in Immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, other

This osteoarthritis review discusses cGAS-STING and NLRP3 signaling in mechanotransduction and mitochondrial danger signal propagation, mechanistically adjacent but not directly tied to SAMHD1 biology or the interferon-mitochondrial syndrome described.
DOI: 10.3389/fimmu.2026.1931112

Liver Organoids: From Disease Modelling to Regenerative Medicine. (from Hepatology/regenerative medicine)
Wang Tiepeng; Qu Xiaotian; Si Jinhong; Meng Junkang; Zhang Ting — Cell proliferation 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general liver organoid review with only a passing mention of prime editing correction in patient-derived organoids and no SAMHD1, interferon, NLRP3, or mitochondrial dNTP pathway content relevant to the family phenotype.
DOI: 10.1111/cpr.70268

Hierarchical Core-Shell Nanoplatform with Sequential Mn<sup>2+</sup>/Co<sup>2+</sup> Release Enables Dual-Track STING Amplification and Radiosensitization for Potent Radio-Metalloimmunotherapy. (from Oncology/nanomedicine radiotherapy)
Luo Baiyi; Xiang Qingming; Xie Yingling; Wang Shuo; Xu Yu — 2026
Score: 3/10 | Pathways: cGAS-STING

Paper uses cGAS-STING pathway activation as a cancer nanomedicine strategy via metal ion delivery, unrelated to SAMHD1 mechanism or mitochondrial dNTP dysregulation despite shared pathway terminology.
DOI: 10.1016/j.actbio.2026.08.012

Estrogen Withdrawal-Induced Cognitive Impairment in Menopausal Women: Mechanisms and Prospects for Integrated Interventions. (from Neurology/Endocrinology)
Qiu Tiantian; Zhang Junying; Zhao Jiayou — International journal of molecular sciences 2026
Score: 3/10 | Pathways: NLRP3, mito-ROS-NF-kB

Discusses NLRP3 inflammasome and mitochondrial dysfunction in menopausal cognitive decline, sharing mechanistic overlap with the interferon-mitochondrial syndrome but unrelated to SAMHD1 or its specific pathways.
DOI: 10.3390/ijms27157003

The APC/C subunit APC7 exerts antiviral effects by targeting the adaptor protein MAVS (from Virology/cell biology (RIG-I-MAVS antiviral signaling))
Rui Su; Aiping Sun; Yifan Niu; Tiesuo Zhao; Hui Wang — Frontiers in Immunology 2026
Score: 3/10 | Pathways: other

This paper concerns RIG-I/MAVS antiviral signaling and IFN-I induction via a distinct APC7-MAVS ubiquitination mechanism, not overlapping with SAMHD1/cGAS-STING/NLRP3/NF-kB pathways central to the disease profile.
DOI: 10.3389/fimmu.2026.1912055

Extracellular vesicle-mediated immune crosstalk in rheumatoid arthritis synovium: mechanistic insights and translational challenges (from Rheumatology)
Feng Luo; Xuemei Yuan; Heng Zhou; Qiuyi Wang; Changming Chen — Frontiers in Immunology 2026
Score: 3/10 | Pathways: cGAS-STING, JAK-STAT, NF-kB-IKK, clinical-phenotype

This RA-focused review touches on cGAS-STING, NF-κB, and JAK-STAT signaling and mentions RA (a tracked family phenotype), but it centers on extracellular vesicle biology in synovium without any connection to SAMHD1, dNTP metabolism, or the core mitochondrial-interferon mechanism.
DOI: 10.3389/fimmu.2026.1891984

Targeting the hallmarks of ageing: Pharmacological challenges and breakthroughs in CRISPR delivery systems and future prospects. (from Gerontology/pharmacology (CRISPR delivery technology))
Rathore Sakshi; Gupta Akash; Shah Kamal; Chauhan Nagendra Singh; Gupta Sanjay Ku — Ageing research reviews 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

General CRISPR delivery/ageing review with only generic mention of prime/base editing and mitochondrial dysfunction, lacking any SAMHD1, immune, or myeloid-specific delivery focus relevant to this disease.
DOI: 10.1016/j.arr.2026.103301

Expanding the clinical spectrum of DNASE1L3-associated monogenic lupus: A case series of 4 syrian pediatric cases. (from Pediatric Rheumatology/Nephrology)
Kousa Alyamama; Alhamwi Ahmad; Alsayed Mohammad Khaled; Jabaly Sara; Khalil Bash — Medicine 2026
Score: 3/10 | Pathways: AGS-spectrum, clinical-phenotype, treatment-target

DNASE1L3 monogenic lupus is a distinct autosomal-recessive nucleic acid clearance disorder in the broader interferonopathy/autoimmune spectrum, but does not involve SAMHD1, dNTPase, cGAS-STING, or the mitochondrial-NLRP3 axis central to this profile, though baricitinib use is a tangential JAK-inhibitor overlap.
DOI: 10.1097/MD.0000000000050283

Pathway Coverage This Week

  • cGAS-STING: 13 papers
  • treatment-target: 13 papers
  • NLRP3: 7 papers
  • prime-editing: 7 papers
  • gene-therapy-delivery: 7 papers
  • NF-kB-IKK: 6 papers
  • other: 6 papers
  • mito-ROS-NF-kB: 4 papers
  • clinical-phenotype: 4 papers
  • POLG-mtDNA: 2 papers
  • urate-NLRP3: 2 papers
  • JAK-STAT: 2 papers
  • VDAC1: 1 papers
  • mito-dNTP-transport: 1 papers
  • ISG15-mitophagy: 1 papers
  • AGS-spectrum: 1 papers

SAMHD1 Research Digest — 2026-08-12

Generated by samhd1_monitor | Model: claude-sonnet-5

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

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

PEG3 inhibits mitophagy of papillary thyroid carcinoma through ISG15/VCP axis (from Oncology (thyroid carcinoma))
Bing Wang; Jing Yao; Zheng Wan; Xin Miao; Zelong Yang — Cellular and Molecular Life Sciences 2026
Score: 7/10 | Pathways: ISG15-mitophagy, treatment-target

This paper directly demonstrates ISG15 binding to and stabilizing VCP to promote mitophagy, providing mechanistic support for the RED pathway (ISG15-mediated mitophagy blockade) in the SAMHD1 interferon-mitochondrial syndrome model, though in a cancer rather than interferonopathy context.
DOI: 10.1007/s00018-026-06368-x

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

Cholesterol Drives IFITM3+ Microglia Activation and Induces STING Mediated Neuroinflammation After Ischemic Stroke. (from Neurology/stroke)
Cheng Yue; Zhou Yuxi; Chen Yonghui; Shen Tianni; Li Yan — CNS neuroscience & therapeutics 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target

This paper demonstrates mitochondrial DNA leakage driving STING-mediated NLRP3 inflammasome activation in microglia via cholesterol-induced IFITM3+ activation, directly paralleling the BLUE/PURPLE loop mechanism (mtDNA fragments → cGAS/STING → inflammation) and using pharmacological STING inhibition (C-176, analogous to therapeutic targets in the SAMHD1 pathway) as a treatment strategy relevant to interferonopathy management.
DOI: 10.1002/cns.71073

cGAS-STING targeting offers a novel therapeutic paradigm in hemorrhagic stroke. (from Neurology/stroke)
Wang Yu; Dou Lidong; Gao Ying; Zhang Ming; Wang Zhiji — Tissue & cell 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target

Reviews cGAS-STING/mtDNA-driven neuroinflammation and NLRP3 activation with pharmacological inhibitors (RU.521, H-151), directly relevant to the BLUE loop mechanism though in a distinct clinical context (hemorrhagic stroke rather than SAMHD1 interferonopathy).
DOI: 10.1016/j.tice.2026.103851

The Role of SAMHD1 in Viral Resistance and Transduction Efficiency Challenges in Pediatric Hematological Malignancies: Mechanistic Insights and Clinical Perspectives. (from Pediatric hematology-oncology / gene therapy)
Alzamzami Waseem — European journal of haematology 2026
Score: 6/10 | Pathways: dNTPase, gene-therapy-delivery, treatment-target, clinical-phenotype

Reviews SAMHD1 dNTPase biology, viral restriction (Vpx), and lentiviral gene therapy transduction barriers relevant to gene correction strategies, though focused on pediatric leukemia rather than A565T haploinsufficiency or interferon-mitochondrial mechanism.
DOI: 10.1111/ejh.70027

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

From xanthine oxidase inhibition to inflammasome regulation: exploring the potential role of allopurinol in TXNIP-NLRP3 signaling and pyroptosis in diabetes. (from Endocrinology/diabetes pharmacology)
Qamar Faiz; Parveen Ramsha; Vaseem Mohd; Ahmad Tufail; Vohora Divya — Inflammopharmacology 2026
Score: 4/10 | Pathways: NLRP3, urate-NLRP3

Reviews xanthine oxidase/TXNIP-NLRP3 pyroptosis in diabetes—touches the GOLD (uric acid-NLRP3) axis conceptually but is disease-context (diabetes) rather than SAMHD1/interferonopathy-driven and offers no mitochondrial dNTP or IFN-I linkage.
DOI: 10.1007/s10787-026-02354-8

Establishment of a scalable engineered cell-line platform for direct, GMP-grade production of eVLP vectors enabling streamlined generation of gene-edited CAR-T/NK cells. (from cell and gene therapy manufacturing/bioengineering)
Lin Wei; Shi Jiaru; Chen Hanyi; Chai Ruikai; Zhu Sha — Frontiers in immunology 2026
Score: 4/10 | Pathways: gene-therapy-delivery

This paper describes an eVLP-based manufacturing platform for CAR-T/NK gene editing, which is only tangentially related to SAMHD1 mechanisms but shares the eVLP delivery technology category noted as relevant to future gene correction strategies.
DOI: 10.3389/fimmu.2026.1878099

Highly efficient CRISPR editing enabled by magnetic nanoparticle delivery. (from biomedical engineering/genome editing methodology)
Go Inkyung; Lee Seung Hwan — Frontiers in genome editing 2026
Score: 3/10 | Pathways: gene-therapy-delivery

This paper describes a general improvement in CRISPR delivery efficiency (magnetofection) without any immune/myeloid-cell specificity, SAMHD1 relevance, or disease pathway connection, making it only tangentially useful as a generic gene-editing delivery method.
DOI: 10.3389/fgeed.2026.1865675

PIWI-piRNA Axis in Epilepsy: Bridging Epigenetic Regulation, Neuroinflammation, and Neuronal Excitability. (from Neurology (epilepsy/epigenetics))
Shyam Mukul; Rashmi Rashmi; Sharma Vidhi; Venkatesh Rajendran; Jain Aditi — Molecular neurobiology 2026
Score: 3/10 | Pathways: NLRP3, other

Discusses NLRP3/TLR4-NF-kB in epilepsy via piRNA epigenetics, a tangential mechanistic overlap but unrelated to SAMHD1, mitochondrial dNTP biology, or interferonopathy, and epilepsy is not a documented family phenotype.
DOI: 10.1007/s12035-026-06103-4

Pathway Coverage This Week

  • treatment-target: 4 papers
  • NLRP3: 4 papers
  • gene-therapy-delivery: 3 papers
  • cGAS-STING: 2 papers
  • ISG15-mitophagy: 1 papers
  • dNTPase: 1 papers
  • clinical-phenotype: 1 papers
  • urate-NLRP3: 1 papers
  • other: 1 papers

SAMHD1 Research Digest — 2026-07-29

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 12 papers evaluated | 3 high-relevance (≥7) | 8 medium (5–6) | 1 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Mitophagy mitigates mitochondrial DNA-induced activation of cGAS-STING in autoimmune thyroiditis (from Endocrinology/Rheumatology—autoimmune thyroiditis model provides orthogonal evidence for cGAS-STING-driven tissue-specific autoimmunity that bridges to systemic interferonopathy phenotype in multi-system SAMHD1 families.)
Xiao-Chen Xie; Yang Guo; Ran Guo; Yong-Ze Li; Shan-Shan Wang — Nature Communications 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, POLG-mtDNA, mito-ROS-NF-kB, treatment-target, clinical-phenotype

Directly demonstrates mtDNA-cGAS-STING axis driving autoimmune disease via impaired mitophagy (PINK1/Parkin/TAX1BP1), mechanistically overlapping with the RED and BLUE loops in SAMHD1 A565T haploinsufficiency; identifies STING inhibition as therapeutic target applicable to convergent interferonopathy.
DOI: 10.1038/s41467-026-76047-9

NLRP3 Inhibitor KBD3536 Attenuates Acute Inflammation, Radiation-Induced Skin Injury, and Early Metabolic Dysfunction in Preclinical Models. (from Pharmacology/medicinal chemistry (NLRP3 inhibitor drug discovery and preclinical efficacy testing))
Qian Xinying; Ye Fei; Li Zhiyong; Chu Hongzhu; Xu Zeng — Pharmaceuticals (Basel, Switzerland) 2026
Score: 7/10 | Pathways: urate-NLRP3, NLRP3, NF-kB-IKK, treatment-target, clinical-phenotype

KBD3536 is a novel NLRP3 inhibitor with demonstrated efficacy in MSU-induced acute inflammation (gouty arthritis) and HFD-induced metabolic dysfunction—two pathologies directly implicated in the SAMHD1 A565T family phenotype (dGTP → purine catabolism → uric acid → MSU-NLRP3 axis; hepatic steatosis via IRF7-metabolic reprogramming); the paper provides preclinical validation of NLRP3 inhibition as a therapeutic strategy for this converged interferonopathy-metabolic syndrome.
DOI: 10.3390/ph19071083

CRISPR screening identifies GNPTAB as a noncanonical STING activator driving cellular senescence. (from Cell biology/gerontology—lysosomal biology and senescence mechanotransduction, not traditionally part of immunology or rheumatology training.)
Yin Jian; Gao Yizhou; Jing Yaobin; Jiang Xiaoyu; Wang Feibo — Protein & cell 2026
Score: 7/10 | Pathways: cGAS-STING, NF-kB-IKK, mTOR-lysosomal, treatment-target

GNPTAB-STING noncanonical activation via direct protein-protein interaction (E1119 interface) provides a novel upstream STING priming mechanism independent of canonical cGAS-mtDNA sensing; this represents an alternative route to STING/TBK1/NF-κB axis hyperactivation relevant to the BLUE and NF-κB crosstalk loops in A565T interferonopathy, with actionable therapeutic potential (STING-GNPTAB interface antagonism) for suppressing senescence-associated STING amplification.
DOI: 10.1093/procel/pwag049

🟡 Medium Relevance (Score 5–6)

Score ≥6 auto-added to Zotero; lower scores: review manually

DNAJB12/14 redox switching directs chaperone- and Bax/Bak-dependent ER protein reflux. (from Cell biology / ER stress and proteostasis; redox biochemistry)
Abu Madegam Laila; Gavriel Noa; Adebisi Raifu Tolulope; Igbaria Aeid — Redox biology 2026
Score: 6/10 | Pathways: BIK-cancer, mTOR-lysosomal, NF-kB-IKK, apoptosis-autophagy switch

BIK-mediated BAX/BAK recruitment to ER during severe ER stress mechanistically overlaps with the apoptosis-autophagy switch dysregulated in SAMHD1 haploinsufficiency, where ISGylation of BH3-only proteins and mitochondrial damage drive cell death; redox-sensitive DNAJB chaperone control of proteostasis and ER-to-cytosol signaling may modulate the severity of interferonopathy-driven ER stress in this family.
DOI: 10.1016/j.redox.2026.104324

Pectolinarigenin Attenuates LPS-Induced Lung Inflammation and Injury with Reduced HDAC3/NF-κB/NLRP3 Signaling. (from Pulmonology/immunotoxicology; plant natural products pharmacology)
Kim Danbee; Lee Dong-Keon; Park Jeong-Ran — Antioxidants (Basel, Switzerland) 2026
Score: 6/10 | Pathways: NLRP3, NF-kB-IKK, NF-kB-NLRP3-priming, treatment-target

Pectolinarigenin directly modulates the HDAC3/NF-κB/NLRP3 axis in LPS-induced inflammation, addressing two key steps in the proband's pathophysiology: NF-κB transcriptional priming of NLRP3 (Signal 1) and NLRP3 inflammasome activation (Signal 2); HDAC3 inhibition is a mechanistically novel approach to breaking the NF-κB–NLRP3 feed-forward loop and reducing mitochondrial ROS-driven inflammation, though the study uses acute LPS challenge rather than the chronic mitochondrial dNTP–oxMtDNA–NLRP3 circuit specific to SAMHD1 haploinsufficiency.
DOI: 10.3390/antiox15070898

Evolutionary history and recombination in the mitochondrial carrier SLC25 superfamily analyzed by similarities in the exon and transmembrane α‐helix sequences (from Evolutionary biology / structural proteomics)
Magnus Monné; D. V. Miniero; R. Calvello; A. Cianciulli; Luigi Palmieri — Protein Science : A Publication of the Protein Society 2026
Score: 6/10 | Pathways: mito-dNTP-transport, nucleotide-rewiring, other

This evolutionary/structural analysis of SLC25 superfamily (including PNC1/PNC2 nucleotide carriers) provides mechanistic foundation for understanding how substrate-specific subfamilies arose, directly relevant to the PNC1/2-mediated mitochondrial dNTP import bypass that drives NLRP3 hyperactivation in SAMHD1 haploinsufficiency; exon recombination patterns could illuminate functional specialization of dNTP transporters.
DOI: 10.1002/pro.70727

Synthetic Toll-Like Receptors for Control of Innate Immunity With Far-Red Light. (from Synthetic optogenetics/photobiology—a tool discipline offering potential mechanistic insight and future targeting strategy for the NF-κB and interferon regulatory axis but without direct mitochondrial, dNTPase, or disease-specific validation.)
Leopold Anna V; Verkhusha Vladislav V — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 6/10 | Pathways: NF-kB-IKK, IRF7-metabolic, treatment-target

Synthetic TLR optogenetics with MyD88→NF-κB/IRF3/IRF7 axis reprogramming is mechanistically adjacent to the NF-κB priming of NLRP3 and the dual IKKε-driven NF-κB + IRF7 crosstalk that sustains the convergent interferon–mitochondrial syndrome in SAMHD1 p.A565T haploinsufficiency; optical dissection of TLR→MyD88→NF-κB/IRF signaling could reveal druggable nodes in the IKK-NEMO complex and IRF7-metabolic amplification loop.
DOI: 10.1002/advs.202520640

Targeting the NLRP3/Caspase-1 pyroptotic pathway exacerbates insulin resistance upon exposure to nanoplastics with different surface chemistries. (from Environmental toxicology and metabolic disease; bridges to rare disease through convergent NLRP3-inflammasome-insulin-resistance axis and mitochondrial dysfunction phenocopy of SAMHD1 haploinsufficiency.)
Yao Xinxin; Cao Yu; Lin Sue; Chen Shihua; Xie Feiqin — Journal of hazardous materials 2026
Score: 6/10 | Pathways: NLRP3, mitochondrial-ROS-NF-kB, oxidative-stress-mtDNA, metabolic-dysfunction-insulin-resistance, inflammasome-pyroptosis, other

Paper demonstrates NLRP3/caspase-1 pyroptotic activation downstream of nanoplastic-induced mitochondrial dysfunction and cytosolic mtDNA accumulation in metabolic stress (hyperglycemia/insulin resistance), directly modeling the PURPLE-loop mechanism (ox-mtDNA → NLRP3) and BLUE-loop (mtDNA escape → inflammasome) operative in SAMHD1 A565T haploinsufficiency; validates NLRP3 inhibition as partial rescue strategy for metabolic phenotypes, but lacks SAMHD1, dNTPase, or dNTP-mediated mechanism, and uses exogenous environmental trigger rather than genetic haploinsufficiency.
DOI: 10.1016/j.jhazmat.2026.143078

Astilbin Alleviates Gouty Arthritis via Regulating NLRP3 Inflammasome and NF-κB Signaling Pathway: A Comprehensive Study on In Vitro and In Vivo Experimental Models. (from Rheumatology/Pharmacology (natural product anti-inflammatory); mechanism-of-action study demonstrating dual NLRP3–NF-κB inhibition in gouty arthritis model, transferable to dNTP-driven NLRP3 hyperactivation in SAMHD1-deficient states.)
Zhang Xiaoxi; Fu Gaoyang; Zhao Xinyu; Huang Yan; Li Fenfen — Nutrients 2026
Score: 6/10 | Pathways: urate-NLRP3, NLRP3, NF-kB-IKK, NF-kB-NLRP3-priming, treatment-target

Astilbin suppresses MSU-crystal–induced NLRP3 inflammasome and NF-κB signaling (P-p65, P-IKKα, P-IκBα, cleaved-caspase-1), directly targeting the GOLD pathway (dGTP → uric acid → MSU → NLRP3) and the NF-κB priming axis that sustains IL-1β autocrine amplification in SAMHD1 haploinsufficiency; relevant as a potential adjunctive therapeutic for the inflammatory arm of convergent interferon–mitochondrial syndrome in this family.
DOI: 10.3390/nu18142360

Blood transcriptome bridges orthogonal immunotypes and gut microbiome enterotypes in humans. (from Microbiome/Metabolomics)
Affaticati Fabio; Ha My K; Gehrmann Thies; De Boeck Ilke; Kuznetsova Mariia — Cell reports 2026
Score: 6/10 | Pathways: NF-kB-IKK, JAK-STAT, NLRP3, clinical-phenotype

Blood transcriptome integration identifies two distinct inflammatory profiles—interferon-driven versus NF-κB/IL-6-driven—that directly map to the divergent activation streams (BLUE interferon loop vs. PURPLE/GOLD NLRP3 loops) in SAMHD1 A565T haploinsufficiency; gut microbiota-immune axis bridging is relevant to family's reported gastrointestinal heterogeneity and immunotype stratification in interferonopathy populations.
DOI: 10.1016/j.celrep.2026.117752

Evaluation of Zebularine as a Potential DNA Methyltransferase 1 Inhibitor Associated With SAMHD1 Expression in Cancer Cells (from Oncology)
Muhammad Zeeshan Ahmed; Mahnoor Fatima; Ayesha Shahbaz; Zeeshan Mutahir — ChemistrySelect 2026
Score: 5/10 | Pathways: BIK-cancer, SAMHD1, treatment-target

Zebularine modulates SAMHD1 expression in prostate cancer cells (relevant to BIK-prostate axis and SAMHD1 as tumor suppressor in family phenotype), but mechanistic connection is via DNMT1 epigenetic silencing rather than dNTPase activity, mitochondrial dysfunction, or interferonopathy pathways central to A565T haploinsufficiency.
DOI: 10.1002/slct.73893

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

VRK3 promotes KSHV infection by suppressing the antiviral type I interferon response. (from Virology/Oncology (KSHV tropism and persistent infection pathogenesis, not immunometabolic or rare disease))
Yu Caroline J; Damania Blossom — PLoS pathogens 2026
Score: 3/10 | Pathways: IRF3, cGAS-STING, JAK-STAT, other

VRK3 suppresses IRF3 and TBK1 activation in KSHV infection, which intersects the cGAS-STING→IRF3→IFN-I axis (BLUE Loop), but lacks SAMHD1 involvement, mitochondrial pathology, dNTP metabolism, NLRP3, or direct relevance to the A565T haploinsufficiency mechanism driving the convergent interferon–mitochondrial syndrome.
DOI: 10.1371/journal.ppat.1014400

Pathway Coverage This Week

  • treatment-target: 7 papers
  • NF-kB-IKK: 7 papers
  • NLRP3: 5 papers
  • cGAS-STING: 3 papers
  • clinical-phenotype: 3 papers
  • other: 3 papers
  • urate-NLRP3: 2 papers
  • mTOR-lysosomal: 2 papers
  • BIK-cancer: 2 papers
  • NF-kB-NLRP3-priming: 2 papers
  • JAK-STAT: 2 papers
  • VDAC1: 1 papers
  • ISG15-mitophagy: 1 papers
  • POLG-mtDNA: 1 papers
  • mito-ROS-NF-kB: 1 papers
  • apoptosis-autophagy switch: 1 papers
  • mito-dNTP-transport: 1 papers
  • nucleotide-rewiring: 1 papers
  • IRF7-metabolic: 1 papers
  • mitochondrial-ROS-NF-kB: 1 papers
  • oxidative-stress-mtDNA: 1 papers
  • metabolic-dysfunction-insulin-resistance: 1 papers
  • inflammasome-pyroptosis: 1 papers
  • SAMHD1: 1 papers
  • IRF3: 1 papers

↩ Re-run 08:33 UTC | Model: claude-sonnet-5

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

🟡 Medium Relevance

Multiple Roles of G3BP1 in Regulating STING-Dependent Interferon and Cytokine Induction by Cytosolic dsDNA and HSV-1 Infection. (from Virology/cell stress biology)
Trupti Devale; Praveen Manivannan; K. Malathi — Viruses 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Details G3BP1 as a regulator of cGAS-STING signaling (STING Golgi trafficking, IFN/cytokine output) directly relevant to the BLUE loop mechanism underlying the SAMHD1 interferonopathy, though it does not involve SAMHD1 itself.
DOI: 10.3390/v18070719