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SAMHD1 Research Digest — 2026-08-02

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 24 papers evaluated | 2 high-relevance (≥7) | 13 medium (5–6) | 9 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Mitochondrial DNA oxidation propagates autoimmunity by enabling plasmacytoid dendritic cells to induce TFH differentiation 2253320 (from Rheumatology/Autoimmunity)
Hongxu Xian; Michael Karin — The Journal of Immunology 2026
Score: 8/10 | Pathways: NLRP3, cGAS-STING, IRF7-metabolic, POLG-mtDNA, NF-kB-NLRP3-priming, clinical-phenotype

Demonstrates that oxidized mtDNA released via NLRP3/caspase-1/gasdermin-D drives pDC-mediated IL-1β and IFN-α signaling to promote TFH differentiation and autoantibody-driven autoimmunity, directly reinforcing the ox-mtDNA-NLRP3-IFN convergence central to the SAMHD1 A565T mechanism and its autoimmune/rheumatologic phenotype spectrum.
DOI: 10.1093/jimmun/vkag141.168

Pannexin1 promotes cellular senescence by triggering mtDNA release to activate the cGAS-STING pathway. (from Nephrology (acute kidney injury/chronic kidney disease and cellular senescence))
Li Jiaqi; Zhao Xin; Shen Yanting; Huang Liuwei; Guo Jie — 2026
Score: 7/10 | Pathways: cGAS-STING, NF-kB-IKK, VDAC1, treatment-target

This paper demonstrates mtDNA release via mPTP/BAX activating cGAS-STING to drive NF-κB-mediated SASP and IRF3 interferon output, directly paralleling the BLUE/Loop A mechanism (mtDNA escape → cGAS → STING → IFN-I plus NF-κB crosstalk) central to the SAMHD1 interferon-mitochondrial syndrome, though in a renal senescence rather than SAMHD1 context.
DOI: 10.1016/j.bbadis.2026.168388

🟡 Medium Relevance (Score 5–6)

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

Diazonium-Enabled Post-Synthetic Construction of Enantiomeric Single-Atom Nanoagents Used for Alzheimer's Disease Treatment. (from Neurology/Nanomedicine)
Ya Junlin; Liu Mengmeng; Ji Yanjun; Tong Zhibo; Luo Bin — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates mtDNA leakage-driven cGAS-STING activation in neuroinflammation and a nanoagent therapeutic strategy directly targeting this core pathway, relevant to the interferon-mitochondrial mechanism though not SAMHD1-specific.
DOI: 10.1002/smll.74610

The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets. (from Cardiology)
Rong Jiaxiang; Wang Zhen; Lin Xiaoxiao; Lei Ziwen; Huang Qianqian — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, mito-ROS-NF-kB, treatment-target, clinical-phenotype

This review synthesizes cGAS-STING, NLRP3, and mitochondrial DAMP-driven inflammatory circuits in cardiovascular disease that mechanistically overlap with the SAMHD1-driven interferon-mitochondrial pathways implicated in the family's cardiac and metabolic phenotypes, though it does not address SAMHD1 directly.
DOI: 10.1002/mco2.70878

Mito-TEMPO attenuates LPS-induced acute lung injury accompanied by ferroptosis suppression and reduced HSP90-STING association. (from Pulmonology/critical care)
Yao Yun; Guo Wei; Tian Yujia; Zeng Lisheng; Xia Xin — International immunopharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, mito-ROS-NF-kB, treatment-target

Demonstrates mitochondrial ROS scavenging (Mito-TEMPO) disrupting STING signaling (via HSP90-STING/TBK1-IRF3) and downstream ferroptosis in acute lung injury, directly paralleling the BLUE pathway's cGAS-STING-IFN axis and mito-ROS/NF-kB crosstalk relevant to interferonopathy-driven mitochondrial damage.
DOI: 10.1016/j.intimp.2026.117210

Modulation of Toll-like receptor driven monocyte activation by JAK-STAT inhibitors in people with HIV. (from Infectious disease/HIV immunology)
Camard Marion; Plaçais Léo; Bitu Marie; Mouanga Christelliah; Bourdic Katia — AIDS (London, England) 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype

Demonstrates JAK-STAT inhibitors (baricitinib, a drug listed as therapeutically relevant) suppressing TLR-driven IFN-I monocyte activation, directly supporting the RED pathway/IFN-JAK-STAT axis therapeutic rationale relevant to SAMHD1 interferonopathy management.
DOI: 10.1097/QAD.0000000000004530

The Autophagy-Inflammasome Axis as a Molecular Switch: From Persistent Inflammation to Vascular Remodeling in IVIG-Resistant Kawasaki Disease. (from Pediatric rheumatology/cardiology (Kawasaki disease vasculitis))
Zhang Rong; Zhang Jiaqi; Yang Yanzhi; Wang Ya; Cao Haijun — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target, clinical-phenotype

Discusses mitophagy dysfunction driving cGAS-STING/NLRP3 inflammasome activation and IL-1β signaling in a pediatric vasculitis, mechanistically parallel to the SAMHD1 interferon-mitochondrial-inflammasome axis but in a distinct clinical context.
DOI: 10.3390/ijms27146405

Rocket-Inspired Sequentially Targeted Nanotherapeutics for Mitochondrial Regulation and Inflammatory Reprogramming in Ischemic Stroke. (from neurology/nanomedicine)
Bai He; Yong Zihao; Li Yang; Chen Qingmin; Liu Yong — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

Demonstrates a Drp1/mtDNA/cGAS-STING axis driving neuroinflammation with a mitochondrial-targeted nanotherapeutic, mechanistically adjacent (mtDNA release/cGAS-STING) though not SAMHD1-specific and in a different disease context (stroke).
DOI: 10.1002/advs.76859

Research Progress on Regulating Neuroinflammation After Spinal Cord Injury by Targeting the cGAS-STING Pathway. (from Neurosurgery/Spinal cord injury)
Xu Nanjian; Ma Weihu; Dong Weixin; Yu Liang — Neuromolecular medicine 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target

Reviews cGAS-STING/mtDNA-driven NLRP3 activation and pyroptosis in neuroinflammation, mechanistically overlapping with Loop A/B and NLRP3 priming/activation core to the SAMHD1 syndrome, though in a spinal cord injury context rather than SAMHD1 disease.
DOI: 10.1007/s12017-026-08938-5

Köhlmeier-Degos disease is an interferonopathy characterized by type I and II interferon-driven inflammatory vasculopathy. (from Dermatology/Vasculopathy (rare disease immunology))
Cudrici Cornelia D; Goel Shubham; Sakamoto Keiko; Jin Seon-Pil; Sekiguchi Akiko — Cell reports. Medicine 2026
Score: 6/10 | Pathways: JAK-STAT, AGS-spectrum, treatment-target, clinical-phenotype

This paper demonstrates a type I/II interferonopathy vasculopathy responsive to JAK inhibition (ruxolitinib), directly paralleling the IFN-I-driven mechanism and JAK inhibitor therapeutic strategy relevant to SAMHD1-mediated interferonopathy, though it does not involve SAMHD1 or mitochondrial dNTP pathways.
DOI: 10.1016/j.xcrm.2026.102947

Exercise alleviates neuroinflammation and cognitive decline in aged mice via hepatic FGF21-driven microglial mitophagy. (from Neurology/Exercise Physiology)
Li Pengda; Wu Tao; Chen Mengjie; Wang Nan; Jia Xiaopeng — 2026
Score: 6/10 | Pathways: cGAS-STING, mTOR-lysosomal, treatment-target

The paper demonstrates cytosolic mtDNA accumulation driving cGAS-STING neuroinflammation and its reversal via AMPK-TFEB-mediated mitophagy, directly paralleling the BLUE loop and mitophagy-block mechanisms central to the SAMHD1 syndrome, though in an aging/exercise context rather than SAMHD1-specific.
DOI: 10.1016/j.bbi.2026.106935

Phase-dependent dynamics of circulating cell-free mitochondrial DNA reflect distinct immunometabolic states (from Infectious disease/tropical medicine (tuberculosis) and pediatric cardiac surgery)
Karen Alessandra Rodrigues; Emilly Henrique dos Santos; Gabriel Acca Barreira; M — Revista do Instituto de Medicina Tropical de São Paulo 2026
Score: 6/10 | Pathways: VDAC1, NLRP3, POLG-mtDNA, clinical-phenotype

Circulating cell-free mtDNA as a DAMP linking mitochondrial damage to innate immune activation is directly relevant to the BLUE/PURPLE loop mechanisms (VDAC1-mediated mtDNA release, NLRP3 activation) even though SAMHD1 is not studied.
DOI: 10.1590/S1678-9946202668048

Mitochondrial peptide MOTS-c suppresses systemic and cardiac inflammasome activation in a diabetic rat model. (from Cardiology/metabolic physiology)
Mills Aimee R; de Souza Antonio; Pham Toan; Mugisho Odunayo O — Experimental physiology 2026
Score: 5/10 | Pathways: NLRP3, urate-NLRP3, treatment-target, other

Demonstrates a mitochondrial-derived peptide suppressing NLRP3 inflammasome activation (with uric acid correlation) in a diabetic cardiac model, relevant as an adjacent NLRP3/mitochondrial dysfunction mechanism and potential therapeutic strategy but not tied to SAMHD1/interferon pathways.
DOI: 10.1113/EP093714

Microglial immunometabolic reprogramming in Alzheimer's disease: From mitochondrial dysfunction and redox imbalance to NLRP3 inflammasome-driven neuroinflammation. (from Neurology/Alzheimer's disease neuroimmunology)
Li Siyu; Jin Juntao; Liu Yingying; Yuan Jing; Dong Yuhan — Journal of Alzheimer's disease : JAD 2026
Score: 5/10 | Pathways: NLRP3, mito-ROS-NF-kB, other

This review addresses mitochondrial dysfunction, oxidized mtDNA, and NLRP3 inflammasome activation in AD microglia, mechanistically overlapping with the PURPLE/GOLD/mito-ROS-NF-kB streams but in a neurodegenerative rather than SAMHD1-interferonopathy context.
DOI: 10.1177/13872877261469862

Prime editing enables drug-controllable T-cell therapies with clinical immunosuppression. (from Hematology/gene therapy engineering)
Bandala-Sanchez Esther; Petley Emma V; Ramsay Kerry; Hilton Adrienne; White Chri — Blood 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery, treatment-target

Demonstrates multiplex prime editing to correct pathogenic immune-dysregulation variants and engineer drug-resistant T-cells, directly relevant as a translational platform for future correction of heterozygous missense mutations like SAMHD1 A565T in immune/myeloid cells, though not disease-specific.
DOI: 10.1182/blood.2026033156

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

FROM ONE-SIZE-FITS-ALL TO ON-DEMAND: PERSONALIZED CRISPR GENE EDITING FOR RARE GENETIC LIVER DISEASES. (from Hepatology/gene therapy)
Anh Tuan Quan — Clinics and research in hepatology and gastroenterology 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This review covers CRISPR/base/prime editing and LNP delivery platforms for monogenic liver diseases, offering only general technological overlap with future SAMHD1 correction strategies but no direct SAMHD1, interferon, or mitochondrial pathway relevance.
DOI: 10.1016/j.clinre.2026.102892

CRISPR application in hematological disorders: from bench to bedside. (from Hematology/gene therapy)
Ladisa Francesco; Morelli Eugenio; Soncini Debora; Garibotto Matteo; Munshi Nikh — Blood advances 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general review of CRISPR/base/prime editing in hematologic diseases with no SAMHD1, interferon, or mitochondrial pathway content, only tangentially relevant as background on editing modalities that could theoretically correct a SAMHD1 missense variant in hematopoietic/myeloid cells.
DOI: 10.1182/bloodadvances.2025017417

Dual Roles of Free Fatty Acids in Gout Pathogenesis: Inflammatory Drivers and Metabolic Mediators. (from Rheumatology/metabolic lipidology)
Lin Na; Shao Chongyu — International journal of rheumatic diseases 2026
Score: 4/10 | Pathways: NLRP3, urate-NLRP3

Discusses FFA-driven NLRP3 activation and MSU crystal gout mechanisms which touch the GOLD pathway (uric acid-NLRP3 axis) but lacks any SAMHD1, interferon, or mitochondrial dNTP connection.
DOI: 10.1111/1756-185x.70799

Extracellular vesicle-mediated immune crosstalk in rheumatoid arthritis synovium: mechanistic insights and translational challenges (from Rheumatology/EV biology)
Feng Luo; Xuemei Yuan; Heng Zhou; Qiuyi Wang; Changming Chen — Frontiers in Immunology 2026
Score: 4/10 | Pathways: NF-kB-IKK, JAK-STAT, cGAS-STING, clinical-phenotype

This review discusses RA synovial EV-mediated NF-κB/JAK-STAT/cGAS-STING signaling, which touches on core interferonopathy pathways and matches the RA family phenotype, but has no direct SAMHD1, mitochondrial dNTP, or NLRP3 mechanistic link.
DOI: 10.3389/fimmu.2026.1891984

Rutin as a multi-target anti-inflammatory phytochemical in arthritic disorders: pharmacological mechanisms and therapeutic potential. (from Rheumatology/phytopharmacology)
Nazir Muhammad Muzammil; Ashraf Asma — Inflammopharmacology 2026
Score: 3/10 | Pathways: NLRP3, urate-NLRP3, NF-kB-IKK, JAK-STAT

This phytochemical review on rutin in arthritis touches tangentially on NLRP3, NF-κB, JAK-STAT, and urate pathways relevant to the GOLD stream and RA/gout family phenotypes, but has no connection to SAMHD1, interferon signaling, or mitochondrial mechanisms.
DOI: 10.1007/s10787-026-02351-x

Nanobody-STING Agonist Reprogram the Tumor Microenvironment and Improve Adoptive Cell Therapy for Solid Tumors 2309144 (from Oncology/immunotherapy)
Neil C. Chada; Alex Lee; H. Frank; Dawn K. Oh; Hannah Ki — The Journal of Immunology 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target

This paper uses a STING agonist to boost tumor immunity in oncology/immunotherapy context, tangential to the SAMHD1 disease's constitutive STING activation pathway but not addressing interferonopathy, SAMHD1, or mitochondrial dysfunction mechanisms.
DOI: 10.1093/jimmun/vkag141.1501

ESCAPE: assigning site-specific activity to covalent ligands in cells by prime editing (from chemical biology/cancer pharmacology)
Tse Jason; Brothers William; Hayward Rachel; Barbas Sabrina; Sheng Kai — preprint (preprint) 2026
Score: 3/10 | Pathways: prime-editing

This paper describes a general prime-editing-based functional genomics platform for covalent ligand characterization in cancer cell lines, unrelated to SAMHD1 biology, interferonopathy, or immune/myeloid gene correction strategies.
DOI: 10.64898/2026.07.28.741261

In vivo reconstruction of the cell lineage history of a developing mouse with DNA Typewriter, from zygote to late organogenesis (from Developmental biology/genomics)
Yu Qi; Kim Haedong; Seidel Sophie; Acosta-Clark James; Martin Beth — preprint (preprint) 2026
Score: 3/10 | Pathways: prime-editing

This paper demonstrates a prime editing-based lineage tracing technology in mouse embryos, which is only tangentially relevant as a general prime editing methodology advance rather than a myeloid/immune-targeted gene correction strategy applicable to SAMHD1 A565T.
DOI: 10.64898/2026.07.29.741625

Poly(I:C) and QS-21 combination suppresses breast tumor growth and metastasis by repolarizing tumor associated macrophages to anti-tumor macrophages. (from oncology/tumor immunology)
Zheng Haoxin; Jin Yanyan; Wang Zixuan; Yang Guang; Li Jianming — European journal of pharmacology 2026
Score: 3/10 | Pathways: JAK-STAT, cGAS-STING, treatment-target

This oncology-immunotherapy paper uses TBK1-IRF3/type I IFN and JAK-STAT signaling in macrophages, which overlaps mechanistically with the interferonopathy axis but is applied to TNBC immunotherapy rather than SAMHD1 biology.
DOI: 10.1016/j.ejphar.2026.179203

Pathway Coverage This Week

  • treatment-target: 14 papers
  • cGAS-STING: 12 papers
  • NLRP3: 9 papers
  • clinical-phenotype: 7 papers
  • JAK-STAT: 5 papers
  • prime-editing: 5 papers
  • NF-kB-IKK: 4 papers
  • mito-ROS-NF-kB: 3 papers
  • other: 3 papers
  • urate-NLRP3: 3 papers
  • gene-therapy-delivery: 3 papers
  • POLG-mtDNA: 2 papers
  • VDAC1: 2 papers
  • IRF7-metabolic: 1 papers
  • NF-kB-NLRP3-priming: 1 papers
  • AGS-spectrum: 1 papers
  • mTOR-lysosomal: 1 papers