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 paperscGAS-STING: 12 papersNLRP3: 8 papersother: 6 papersISG15-mitophagy: 5 papersurate-NLRP3: 5 papersNF-kB-IKK: 4 papersclinical-phenotype: 4 papersgene-therapy-delivery: 4 papersmito-ROS-NF-kB: 3 papersprime-editing: 3 papersJAK-STAT: 2 papersPOLG-mtDNA: 2 papersME-CFS: 2 papersNF-kB-NLRP3-priming: 2 papersVDAC1: 1 papersdNTPase: 1 papers