Skip to content

SAMHD1 Research Digest — 2026-07-26

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 31 papers evaluated | 5 high-relevance (≥7) | 16 medium (5–6) | 10 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Modeling calcific aortic valve disease with engineered human valve tissues identifies SAMHD1 as a therapeutic target. (from Cardiology/bioengineering (tissue engineering and valvular calcification))
Meng Xiangfu; Zhou Qian; Zhu Zijin; Qiao Weihua; Geng Bingchuan — Biomaterials 2026
Score: 7/10 | Pathways: treatment-target, clinical-phenotype, other

This paper identifies SAMHD1 as a novel therapeutic target in calcific aortic valve disease via WGCNA-driven small-molecule inhibition, extending SAMHD1's disease relevance beyond interferonopathy into a cardiovascular/osteogenic context pertinent to potential cardiac phenotypes in the family.
DOI: 10.1016/j.biomaterials.2026.124432

The mitochondrial DNA signal in rheumatoid arthritis: From metabolic victim to inflammatory driver. (from Rheumatology)
Zhang Ruoyi; Song Zhijie; Xin Qimeng; Xing Wenbin; Zhang Wenlan — Biochemical and biophysical research communications 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, clinical-phenotype, treatment-target

Reviews the mtDNA damage-release-cGAS/STING-NLRP3 axis driving RA inflammation, mechanistically parallel to the purple/blue loops in the SAMHD1 syndrome and directly relevant to the family's rheumatoid arthritis phenotype.
DOI: 10.1016/j.bbrc.2026.154304

Case of Aicardi-Goutières syndrome diagnosed in adulthood on whole-genome sequencing. (from Neurology/Genetics)
Cobb Lewis; Kumar Jayant; Roy Amit; Walsh Sarah; Sheerin Una-Marie — BMJ neurology open 2026
Score: 7/10 | Pathways: AGS-spectrum, cGAS-STING, JAK-STAT, treatment-target, clinical-phenotype

This adult-diagnosed ADAR-related AGS case with atypical presentation, cardiac calcification, and baricitinib consideration directly parallels the type I interferonopathy spectrum and JAK inhibitor treatment strategy relevant to SAMHD1-driven disease.
DOI: 10.1136/bmjno-2025-001407

HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway. (from Virology/hematology (HTLV-1-associated leukemia and neuroinflammatory disease))
Mohanty Suchitra; Suklabaidya Sujit; Mnatsakanyan Nelli; Jacobson Steven; Harhaj — Autophagy 2026
Score: 7/10 | Pathways: cGAS-STING, ISG15-mitophagy, NF-kB-IKK, treatment-target

This paper demonstrates PINK1-PRKN-dependent mitophagy (via NEMO/IKK interaction) suppressing cGAS-STING1-driven type I interferon activation in a viral infection context, directly paralleling the mitophagy-block/IFN-I-amplification mechanism central to the SAMHD1 syndrome model (RED/BLUE loops) even though the driver here is HTLV-1 Tax rather than SAMHD1 dysfunction.
DOI: 10.1080/15548627.2026.2707897

Type I interferonopathies: 15 years after the concept-news and views. (from Rheumatology)
S. Khaldi-Plassart; I. Melki; M. Frémond — Current opinion in rheumatology 2026
Score: 7/10 | Pathways: cGAS-STING, AGS-spectrum, treatment-target, clinical-phenotype, JAK-STAT

This review covers type I interferonopathy mechanisms (STING/IFNAR signaling, TLR pathways, clinical penetrance variability, JAK inhibitor therapeutics) directly relevant to the SAMHD1-driven IFN-I overproduction and AGS-spectrum disorder underlying the family syndrome, though it does not address SAMHD1 specifically.
DOI: 10.1097/BOR.0000000000001179

🟡 Medium Relevance (Score 5–6)

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

Fibroblast S1PR2 Amplifies NLRP3 Inflammasome Activation Under Pressure Overload. (from Cardiology)
Zhou Caixia; Liu Zhihao; Wang Zhiru; Cui Zekun; Wang Qian — Hypertension (Dallas, Tex. : 1979) 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

Demonstrates mitochondrial damage (DRP1 fission, mitophagy suppression) driving mtDNA leakage and NLRP3 activation, mechanistically parallel to the SAMHD1 mitochondrial-inflammasome axis though in cardiac fibroblasts rather than SAMHD1-deficient immune cells.
DOI: 10.1161/HYPERTENSIONAHA.126.27475

Isoalantolactone targets NLRP3 to disrupt NLRP3-NEK7 interaction and suppress inflammasome activation. (from pharmacology/drug discovery)
Shi Yuanfang; Zhu Xiaoyun; Sun Meng; Yang Yang; Lin Siwei — Biochemical pharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

This paper identifies a small-molecule NLRP3 inhibitor effective against MSU-induced gout and MASLD, directly relevant to the GOLD pathway (dGTP→uric acid→MSU→NLRP3) and offering a potential therapeutic candidate for the syndrome's inflammasome-driven pathology.
DOI: 10.1016/j.bcp.2026.118165

Interferon-related gene expression defines disease activity, organ involvement and treatment response in juvenile dermatomyositis. (from Pediatric rheumatology (juvenile dermatomyositis))
Codes-Méndez Helena; Cuyx Senne; Syntakas Aris E; Barmpakou Afroditi; Moraitis E — Rheumatology (Oxford, England) 2026
Score: 6/10 | Pathways: JAK-STAT, treatment-target, clinical-phenotype

Demonstrates type-I interferon-related gene expression (ISGs, IFI27, IFI44L, RSAD2) as biomarker of disease activity and JAK inhibitor (baricitinib) response, directly reinforcing the IFN-I/JAK-STAT arm of the interferonopathy mechanism relevant to SAMHD1 pathway and treatment translation, though not SAMHD1-specific.
DOI: 10.1093/rheumatology/keag384

Glycerol-3-Phosphate Attenuates Hypoxic-Ischemic Brain Injury via Modulation of Microglia-Mediated Neuroinflammation. (from Neurology/perinatal neonatology)
Qin Dani; Lei Yong; Le Meini; Cheng Mengke; Zhao Yingmin — Neurochemical research 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target, mito-ROS-NF-kB

Demonstrates cGAS-STING-TBK1-NF-kB axis driving microglial neuroinflammation and mitochondrial dysfunction, directly relevant to the same core pathway implicated in the SAMHD1 A565T interferon-mitochondrial syndrome, with therapeutic implications for neuroinflammatory phenotypes seen in the family (AuDHD, ME/CFS-like fatigue).
DOI: 10.1007/s11064-026-04848-x

Aspirin Inhibits the cGAS-STING Signaling Pathway to Ameliorate the Development of Aortic Aneurysm and Dissection. (from Vascular surgery/cardiology (aortic aneurysm and dissection))
Zeng Yi-Fan; Wang Qiu-Guo; Qi Zhen; Li Jing-Yu; Duan Zhi-Cheng — Arteriosclerosis, thrombosis, and vascular biology 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates a novel cGAS-STING axis (via cGAS acetylation) driving mitochondrial/ferroptotic vascular pathology and its pharmacological inhibition by aspirin, directly relevant to the Blue loop mechanism though in a cardiovascular rather than immune context.
DOI: 10.1161/ATVBAHA.126.324930

Single-Cell Analysis of Residual Esophageal Squamous Cell Carcinoma After Neoadjuvant Immunochemotherapy Reveals TFAM-Mediated Immunoregulation in Dendritic Cells. (from Oncology (esophageal squamous cell carcinoma immunotherapy))
Chen Linyan; Feng Tang; Zhou Jianfeng; Zeng Hao; Lai Yutian — Cancer research 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

This paper demonstrates TFAM deficiency in dendritic cells activating the STING-TBK1-IRF3 pathway to promote anti-tumor immunity, directly relevant to the mitochondrial-cGAS-STING-IFN-I axis central to the SAMHD1 mechanism though in an oncologic rather than interferonopathy context.
DOI: 10.1158/0008-5472.CAN-25-4738

Stub1 promotes chaperone-mediated autophagy to suppress antiviral immunity. (from Virology/cell biology (autophagy regulation))
Liu Hongyang; Huang Li; Weng Changjiang — Autophagy 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, treatment-target

This paper describes a novel TBK1 degradation pathway (CMA via Stub1) that directly regulates the cGAS-STING-TBK1-IFN-I axis central to the SAMHD1 mechanism, relevant to interferonopathy modulation though not SAMHD1-specific.
DOI: 10.1080/15548627.2026.2667376

Dual-regulation of mitophagy and cytosolic mtDNA-induced inflammation for the treatment of inflammatory bone loss. (from orthopedics/bone regeneration)
Zheng Kaiwen; Che Benchi; Cui Yongzhi; Yang Han; Xiang Yu — 2026
Score: 6/10 | Pathways: cGAS-STING, ISG15-mitophagy, treatment-target, clinical-phenotype

Directly models the mtDNA-cGAS-STING-inflammation-mitophagy (PINK1) axis central to the BLUE/RED streams and demonstrates a dual STING/PINK1 exosome therapeutic, relevant to osteoporosis noted in family phenotype tracking though not SAMHD1-specific.
DOI: 10.1016/j.freeradbiomed.2026.07.031

Tumor microenvironment-responsive manganese nanoplatform amplifies cGAS-STING via metabolic-metal synergy for immunotherapy. (from Oncology/nanomedicine)
Zhou Yanlin; Wu Ziyi; Zheng Tao; Luo Shunhong; Zhang Lu — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates mitochondrial fragmentation-driven mtDNA leakage activating cGAS-STING (mirroring the BLUE/VDAC1 loop) in an oncology nanomedicine context, offering mechanistic and therapeutic parallels though not SAMHD1-specific.
DOI: 10.1016/j.jconrel.2026.115197

Mitochondria-targeted MXene-based nanozymes promote mitophagy and inhibit mtDNA-triggered cGAS/STING inflammation in osteoarthritis. (from Orthopedics/Nanomedicine)
Li Tiancheng; Zheng Ao; Zhu Cheng; Li Yixin; Yang Zitong — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Demonstrates a nanozyme therapeutic that restores mitophagy and blocks mtDNA-driven cGAS/STING inflammation, directly reinforcing the disease model's Loop A mechanism though in an unrelated joint disease context.
DOI: 10.1016/j.bioactmat.2026.07.010

Engineering-Modulated Molybdenum Enzymes Strategy for Tumor-Specific Metabolic-Immunotherapy. (from oncology/nanomedicine)
Pan Xiaoxiao; Pei Zifan; Wu Jie; Jiang Nan; Li Qian — 2026
Score: 6/10 | Pathways: cGAS-STING, urate-NLRP3, treatment-target

This oncology nanomedicine paper demonstrates mtDNA release activating cGAS-STING and purine metabolism driving uric acid elevation as an immune activator, mechanistically paralleling the PURPLE/GOLD and BLUE streams (dGTP-uric acid-MSU-NLRP3 and mtDNA-cGAS-STING) in the SAMHD1 syndrome despite being applied in a cancer immunotherapy context.
DOI: 10.1002/advs.76726

Phase-dependent dynamics of circulating cell-free mitochondrial DNA reflect distinct immunometabolic states (from Tropical medicine/infectious disease and pediatric cardiac surgery biomarker research)
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, treatment-target, clinical-phenotype

Circulating cell-free mtDNA as a DAMP driving innate immune activation is directly relevant to the BLUE/PURPLE mitochondrial escape and NLRP3 activation loops central to the SAMHD1 interferon-mitochondrial syndrome, though it does not address SAMHD1 itself.
DOI: 10.1590/s1678-9946202668048

Severe Antenatal Presentation of a Novel Dnase2 Mutation in a Preterm Omani Neonate: Expanding the Clinical Spectrum of an Ultra-Rare Interferonopathy (from Neonatology/Pediatric Genetics)
Ruqaiya Al Jashmi; Marya Al Barumi; S. Al Abrawi; Alyaa Al Mughairy; Aiman Al Ja — Cureus 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, clinical-phenotype, pregnancy-fetal, treatment-target

DNASE2 deficiency is a type I interferonopathy in the same AGS-spectrum family of diseases as SAMHD1 mutations, sharing cGAS-STING-driven IFN-I pathology and JAK inhibitor responsiveness, with fetal/neonatal presentation relevant to the pregnancy-interferonopathy phenotype tracking axis.
DOI: 10.7759/cureus.111043

Sex-specific differences of amlexanox in a mouse model for atherosclerosis and MASLD. (from Cardiometabolic/hepatology research on IKKε inhibition)
Mungo Eleonora; Haß Michelle; Benning Denis; Schmid Tobias; Kuntschar Silvia — Molecular metabolism 2026
Score: 5/10 | Pathways: NF-kB-IKK, clinical-phenotype

IKKε (a kinase explicitly named in the NF-κB crosstalk mechanism as dual NF-κB/IRF3 activator) is targeted pharmacologically here, showing sex-specific metabolic/inflammatory effects on MASLD and atherosclerosis, relevant background to the IKKβ/IKKε axis but without SAMHD1 or interferon pathway data.
DOI: 10.1016/j.molmet.2026.102426

Editing Around the Target: Epitope Engineering to Protect Stem Cell Grafts. (from Gene therapy/hematology-oncology)
Baek Joanne; Casirati Gabriele; Genovese Pietro; Gill Saar I — Blood advances 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Reviews base/prime editing epitope engineering in HSPCs, relevant as a generic delivery/correction platform potentially applicable to correcting SAMHD1 missense variants in myeloid cells but not disease-specific.
DOI: 10.1182/bloodadvances.2025018227

Efficient CRISPR/Cas9-mediated homology independent sequence replacement in vivo and non-dividing primary cells (from genome editing / gene therapy engineering)
Dang Tu Ngoc; Roman Alexandra; Zimmer Anja; Lebedin Mikhail; Bahry Ella — preprint (preprint) 2026
Score: 5/10 | Pathways: gene-therapy-delivery, prime-editing

This paper describes a novel homology-independent CRISPR/Cas9 sequence replacement platform (REPLACE) using eVLP/AAV delivery in non-dividing cells, relevant as a general gene correction strategy applicable to correcting missense variants like SAMHD1 A565T though not directly tested on it.
DOI: 10.64898/2026.07.24.740048

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Alopecia areata: Mechanisms, targeted therapies, and translational challenges. (from Dermatology)
Kumar Virender; Sahoo Saurabh; Kumar Pawan — Current opinion in pharmacology 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

AA pathogenesis and JAK inhibitor therapy (baricitinib) overlap mechanistically with the IFN-I/JAK-STAT axis relevant to SAMHD1 interferonopathy, but the paper is otherwise unrelated to SAMHD1 or mitochondrial-inflammasome mechanisms.
DOI: 10.1016/j.coph.2026.102635

Gene therapy approaches for inborn errors of immunity: from bench to bedside. (from gene therapy/genetic medicine)
Dara Jasmeen; Booth Claire — Expert opinion on biological therapy 2026
Score: 4/10 | Pathways: gene-therapy-delivery

General review of gene therapy for inborn errors of immunity (retroviral, lentiviral, CRISPR, base/prime editing) provides background relevance to future correction strategies for SAMHD1 variants but has no disease-specific or mechanistic content.
DOI: 10.1080/14712598.2026.2710870

Mitochondrial stress-induced cuproptosis: a metabolic bridge to reprogramming the GBM immune microenvironment. (from Oncology (neuro-oncology/GBM immunotherapy))
Li Wenyang; Lv Yaqing; Wang Guanrong; Lan Xiaolei; Ren Leina — 2026
Score: 4/10 | Pathways: cGAS-STING, other

Discusses mtDNA release triggering cGAS-STING/type I IFN in GBM cuproptosis context, sharing a core mechanistic node but unrelated to SAMHD1 dNTPase biology or the family phenotype spectrum.
DOI: 10.1007/s13402-026-01254-x

Prime editing in neuropsychiatric disorders: From mutation‐specific target selection to clinical translation (from Neurology/gene therapy)
Tianshan Ji; Yuan Zhang; Jinyi Zhao; Yi Lu; Chengkun Wang — Neuroprotection 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

General review of prime editing for neuropsychiatric monogenic disorders offers relevant delivery/technology context but no direct SAMHD1, immune, or mitochondrial pathway content and focuses on neurons rather than myeloid/immune cells.
DOI: 10.1002/nep3.70041

A poly(I:C)/QS-21-based in situ vaccine synergizes with anti-PD-1 therapy to overcome tumor immunoresistance. (from oncology/cancer immunotherapy)
Zhang Wenbo; Ni Xinrui; Zhuo Luoyi; Liu Jiangrui; Yang Guang — Cell reports. Medicine 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target

This oncology immunotherapy paper touches TBK1-IRF3-type I interferon axis (relevant pathway component) but in a tumor vaccine/anti-PD-1 context unrelated to SAMHD1 haploinsufficiency or the family's interferonopathy syndrome.
DOI: 10.1016/j.xcrm.2026.102932

Gene/Genome Editing in Cardiovascular Biology and Disease. (from Cardiology/gene therapy)
Verma Tushar; Singh Ravi Pratap; Chaudhary Mahima; Sharma Pramod Kumar; Kumar Dh — Current gene therapy 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general cardiovascular gene-editing review with no connection to SAMHD1, interferon-mitochondrial mechanisms, or myeloid/immune cell editing relevant to the family syndrome.
DOI: 10.2174/0115665232453929260206091608

Mitochondrial Communication Networks in the Bone Microenvironment: From the Maintenance of Homeostasis to Translational Interventions for Bone Diseases. (from Orthopedics/bone biology)
Wang Wentao; Wang Kun; Wang Wenjing; Mu Xuan; Cheng Zhiquan — 2026
Score: 3/10 | Pathways: cGAS-STING, other

Bone microenvironment mitochondrial transfer review touches cGAS-STING/mtDNA release but is focused on osteoporosis/osteoarthritis biology largely tangential to SAMHD1 interferonopathy mechanism.
DOI: 10.1007/s12015-026-11190-w

An Insight into the cGAS-STING Pathway Modulation by Metal Complexes to Initiate Immunogenic Cell Death in Cancer. (from medicinal chemistry/oncology)
Shilpendu Ghosh; Sujato Mukherjee; Arindam Mukherjee — Journal of medicinal chemistry 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target

Discusses cGAS-STING pathway modulation via metal complexes for cancer immunotherapy, mechanistically relevant to Loop A but focused on oncology drug design rather than SAMHD1 or the family syndrome.
DOI: 10.1021/acs.jmedchem.6c00727

Caloric restriction enhances radiosensitivity of colorectal tumors through the cGAS-STING pathway activation. (from Oncology/radiation biology)
Li-Li Zhang; Li-Qiang Qin; Li Ding; Wenyue Shan; Yu Zhao — Cancer & metabolism 2026
Score: 3/10 | Pathways: cGAS-STING

This paper studies cGAS-STING pathway activation via caloric restriction to enhance radiosensitivity in colorectal cancer, sharing a core pathway but in an oncology/radiotherapy context unrelated to SAMHD1 dysfunction, mitochondrial dNTP dysregulation, or the interferonopathy syndrome described.
DOI: 10.1186/s40170-026-00449-y

From convergence to an iterative Optimization-Circumvention-Collapse framework in CRISPR bioengineering (from bioengineering/education)
Federico Filippone-Thaulero — Journal of High School Science 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

General theoretical review of CRISPR/base/prime editing trade-offs from a high school science journal, with no immune/myeloid cell specificity or SAMHD1 relevance beyond generic gene-editing correction strategy context.
DOI: 10.64336/001c.165176

Pathway Coverage This Week

  • treatment-target: 21 papers
  • cGAS-STING: 18 papers
  • clinical-phenotype: 9 papers
  • JAK-STAT: 6 papers
  • gene-therapy-delivery: 6 papers
  • prime-editing: 5 papers
  • other: 4 papers
  • NLRP3: 4 papers
  • AGS-spectrum: 3 papers
  • NF-kB-IKK: 3 papers
  • ISG15-mitophagy: 2 papers
  • mito-ROS-NF-kB: 2 papers
  • urate-NLRP3: 2 papers
  • POLG-mtDNA: 1 papers
  • VDAC1: 1 papers
  • pregnancy-fetal: 1 papers