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

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🔴 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 Mn²⁺/Co²⁺ 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

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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