SAMHD1 Research Digest — 2026-09-16¶
Generated by samhd1_monitor | Model: claude-sonnet-5
Summary: 26 papers evaluated | 2 high-relevance (≥7) | 11 medium (5–6) | 13 low (3–4) | 0 scored <3
🔴 High Relevance (Score 7–10)¶
Auto-added to Zotero (threshold ≥6)
NMN Mitigates LPS-Induced Liver Injury by Inhibiting Ferroptosis via Suppression of the cGAS-STING-ACSL4 Axis. (from Hepatology/sepsis pharmacology)
Liao Yan; Zhu Cheng-Long; Zhang Wangzheqi; Cheng Lin-Dong; Liu Yang — 2026
Score: 7/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype
Demonstrates mtDNA-driven cGAS-STING activation causing ferroptosis and liver injury, directly mirroring the BLUE loop mechanism (VDAC1/mtDNA-cGAS-STING-IFN) and NMN as a potential therapeutic modulator relevant to hepatic phenotypes in the family.
DOI: 10.1016/j.phrs.2026.108454
MA-5 attenuates disease-associated transcriptomic aging and pathological microglial states in Gaucher disease (from Neurodegeneration/lysosomal storage disease (Gaucher/Parkinson's) research)
Abe Takaaki; Tongu Yoshiyasu; Kasahara Tomoko; Nakamura Kohta; Tyshkovskiy Alexa — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target
This paper demonstrates a mitochondrial cristae disruption → mtDNA release → cGAS-STING → NLRP3 inflammasome axis driving neuroinflammation in a lysosomal storage disorder, mechanistically parallel to the BLUE/Loop A pathway in SAMHD1 pathology, with a mitochondria-targeting therapeutic (MA-5) that could inform treatment strategies for interferon-mitochondrial syndromes.
DOI: 10.21203/rs.3.rs-10994808/v1
🟡 Medium Relevance (Score 5–6)¶
Score ≥6 auto-added to Zotero; lower scores: review manually
NAD<sup>+</sup> Metabolic Reprogramming Drives CD8<sup>+</sup> T Cells Senescence and Exacerbates Ulcerative Colitis. (from Gastroenterology/immunosenescence)
Ye Maolin; Zhou Qi; Kong Mingjia; Zhao Suhan; Lin Lingxi — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype
Demonstrates mtDNA leakage activating cGAS-STING to drive immune cell senescence and inflammation in UC, mechanistically paralleling the BLUE loop pathway relevant to SAMHD1-driven interferonopathy though not SAMHD1-specific.
DOI: 10.1111/acel.70706
DNA-PKcs and PARP1 at the interface between DNA damage responses and cGAS-STING signaling: context-dependent roles and therapeutic implications. (from DNA damage repair / oncology pharmacology)
Miao Tiantian; Zhao Jiaqi; Wu Jinghong; Hou Jiabao; Ma Teng — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target
Reviews how DDR factors (DNA-PKcs, PARP1) modulate cGAS-STING signaling, paralleling SAMHD1's own dual role in genome maintenance and innate immune restraint, with therapeutic inhibitor implications relevant to interferonopathy management.
DOI: 10.1080/15384047.2026.2728335
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
This review details IRF1/3/5/7 downstream of cGAS-STING/NF-kB/NLRP3 driving vascular inflammation, offering a plausible cardiovascular manifestation pathway relevant to the IFN-mitochondrial syndrome's cardiology dimension, though it does not mention SAMHD1 directly.
DOI: 10.3390/ijms27177647
Mitochondrial DNA Sensing Reshapes the Tumor Immune Microenvironment via Cooperative cGAS-STING Activation and Ferroptosis (from Oncology/tumor immunology)
Gang Liu; Jia Wang; Li-Qiang An — Global Health Care 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, treatment-target
Demonstrates mtDNA release activating cGAS-STING/IFN-I signaling and downstream inflammatory crosstalk, mechanistically overlapping with BLUE loop pathway even though studied in an oncology/ferroptosis context rather than SAMHD1 haploinsufficiency directly.
DOI: 10.63808/ghc.v2i1.524
The bidirectional immunoregulatory effects of Traditional Chinese Medicine on the cGAS-STING signaling pathway and their translational prospects. (from Traditional Chinese Medicine / pharmacognosy)
Yang Yi; Sun Yiheng; Cheng Yuxiang; Pan Ziteng; Zhou Jing — Chinese medicine 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, treatment-target
Reviews cGAS-STING pathway modulation (including crosstalk with NF-kB/NLRP3 and mitochondrial DNA release) and highlights pharmacological targeting strategies directly relevant to the interferon-mitochondrial axis central to this SAMHD1 syndrome, though it lacks SAMHD1-specific data.
DOI: 10.1186/s13020-026-01494-x
Beyond the Prevention of Anti-drug Antibody Formation with Uricase Therapy: Mechanistic Roles of DMARDs in Modifying Gout Flare Risk. (from Rheumatology/gout pharmacotherapy)
Mikuls Ted R; Neogi Tuhina; Gaffo Angelo — BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target
This review discusses NLRP3 inflammasome activation by MSU crystals and DMARD modulation of that pathway, directly relevant to the GOLD stream (dGTP→purine catabolism→uric acid→MSU crystals→NLRP3) and to family members with gout/rheumatoid arthritis phenotypes.
DOI: 10.1007/s40259-026-00808-7
Baicalein-loaded rhamnolipid nanomicelles target mitochondrial dysfunction and activate the cGAS-STING pathway for triple-negative breast cancer therapy. (from Oncology/nanomedicine)
Wang Nan; Ma Shiyu; Jiao Fangyu; Yu Zhe; Fei Fengshu — Colloids and surfaces. B, Biointerfaces 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, mito-ROS-NF-kB, treatment-target
Demonstrates mitochondrial damage (mtROS, mtDNA release) activating cGAS-STING-TBK1-IRF3-NF-kB axis in cancer therapy, mechanistically overlapping with BLUE loop pathway though in an oncology nanomedicine context rather than SAMHD1-driven interferonopathy.
DOI: 10.1016/j.colsurfb.2026.116173
Crosstalk between innate immune signaling pathways and integrated TLR, NLRP3 inflammasome, cGAS–STING, and NF-κB networks in sepsis (from critical care/sepsis medicine)
Xiao-Xi Du; Han-Chua Qiao — Frontiers in Cell and Developmental Biology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, NF-kB-IKK, NF-kB-NLRP3-priming, mito-ROS-NF-kB, treatment-target
This sepsis-focused review synthesizes the exact TLR/NLRP3/cGAS-STING/NF-kB crosstalk architecture (priming, IKK kinases, ROS-driven amplification) central to the SAMHD1 interferon-mitochondrial mechanism, though not disease-specific.
DOI: 10.3389/fcell.2026.1935200
Neuroimmune interactions: from molecular mechanisms to therapeutic targets. (from Neurology/Neuroimmunology)
Hao Yi-Hang; Shi Rong-Jia; Tang Ya-Ling; Liang Xin-Hua — 2026
Score: 6/10 | Pathways: NLRP3, NF-kB-IKK, JAK-STAT, treatment-target
This general neuroimmune review covers NLRP3/NF-kB/JAK-STAT signaling and CNS-immune crosstalk relevant to the proband's ASD/ADHD and ME/CFS phenotypes, but lacks any SAMHD1-specific or interferonopathy-specific mechanistic detail.
DOI: 10.1186/s43556-026-00565-7
Autophagy determines the fate of immune cells by regulating metabolic remodeling and PANoptosis (Review). (from Autoimmune disease/tumor immunology and cell death biology)
Guo Yanan; Zhou Xinyue; Tian Yixiao; Chen Dan; Xie Xiaofeng — 2026
Score: 6/10 | Pathways: ISG15-mitophagy, NLRP3, VDAC1, treatment-target
This review on autophagy/mitophagy regulating PANoptosis via mtDNA and ROS danger-signal clearance is mechanistically adjacent to the RED/BLUE loop mitophagy block and NLRP3 activation central to the SAMHD1 A565T interferon-mitochondrial syndrome, though it contains no SAMHD1-specific data.
DOI: 10.3892/ijmm.2026.5978
The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets. (from ubiquitin biology/molecular immunology)
Hu Junying; Liu Xingchen; Zhou Wenqiao; Zhong Bing; Liu Feng — 2026
Score: 5/10 | Pathways: NF-kB-IKK, NF-kB-NLRP3-priming, treatment-target
A20 is a key negative regulator of NF-kB/ubiquitin signaling termination directly relevant to the NF-kB-NLRP3 priming crosstalk axis in the SAMHD1 model, but the paper is a general mechanistic review with no SAMHD1, interferon, or mitochondrial dNTP content.
DOI: 10.1186/s43556-026-00557-7
🟢 Low Relevance (Score 3–4)¶
Potential specialty bridges — skim titles
Upadacitinib Restrains the Pathogenic Fitness of CD4<sup>+</sup> T Cells and Aberrant B Cell Programming in Optic Neuritis. (from Neuroimmunology/Ophthalmology)
Jiang Gengchen; Jiang Qi; Han Lian; Peng Yue; Liu Xingyu — 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target
Demonstrates JAK1/STAT3-mediated CD4+ T cell metabolic rewiring and B cell crosstalk in optic neuritis responsive to upadacitinib, relevant only tangentially via shared JAK-STAT/IFN-adjacent signaling and JAK inhibitor treatment relevance rather than SAMHD1-specific mechanism.
DOI: 10.1002/advs.77701
Neutrophil-dependent interferonopathy contributes to joint damage in hemophilia. (from Hematology/Rheumatology (hemophilic arthropathy))
T. Kaminski; N. Swendrowski; O. Katoch; S. Triulzi; R. Vats — Blood 2026
Score: 4/10 | Pathways: JAK-STAT, clinical-phenotype
Demonstrates type-I interferon-driven neutrophil NETosis contributing to joint damage in hemophilia, showing a peripheral disease-relevant example of IFN-I signaling causing tissue pathology but with no direct SAMHD1, cGAS-STING, or NLRP3 mechanistic link.
DOI: 10.1182/blood.2026034670
Interface between inborn errors of immunity and rheumatological disorders in children: A pediatrician's conundrum. (from Pediatric Rheumatology)
Thangaraj Abarna; Aggarwal Ridhima; Sarkar Soumyadeep; Pilania Rakesh Kumar — 2026
Score: 4/10 | Pathways: clinical-phenotype, AGS-spectrum, IRF7-metabolic
General pediatric rheumatology review of inborn errors of immunity that broadly touches on interferon dysregulation and autoimmunity but does not specifically address SAMHD1, its mechanistic pathways, or the family phenotype spectrum.
DOI: 10.5409/wjcp.118174
Clinical and laboratory manifestations and treatment of children with <i>TNFRSF1A</i> gene variants. (from Pediatric rheumatology/autoinflammatory disease)
Alexeeva Ekaterina I; Shingarova Meiri Sh; Dvoryakovskaya Tatyana M; Isaeva Ksen — 2026
Score: 3/10 | Pathways: NLRP3, clinical-phenotype, other
TRAPS/TNFRSF1A is a distinct autoinflammatory monogenic disease with TNF-receptor and NF-kB-adjacent mechanisms that overlaps only superficially (autoinflammation, joint/rheum phenotype) with the SAMHD1 interferonopathy-mitochondrial syndrome, offering limited direct mechanistic relevance.
DOI: 10.5409/wjcp.119428
Nanomaterial-Based Strategies Targeting IL-1 Signalling in Inflammatory Bowel Disease: Therapeutic Applications and Mechanistic Insights. (from Nanomedicine/Gastroenterology)
Wang Kexin; Chen Siyan; Zhang Jiaqi; Du Jiayi; Liu Yiruo — 2026
Score: 3/10 | Pathways: NLRP3, NF-kB-IKK, treatment-target
Reviews nanomaterial drug-delivery strategies for IL-1/NLRP3 in IBD, touching on relevant inflammatory pathways but with no connection to SAMHD1, interferonopathy, or mitochondrial mechanisms.
DOI: 10.2147/jir.s596248
A Defect-Engineered Sono-Piezocatalytic In Situ Hydrogel for Preventing Hepatocellular Carcinoma Recurrence After Incomplete Radiofrequency Ablation. (from Oncology/biomedical engineering (nanomedicine, interventional radiology))
Ke Jianji; Liu Feiqi; Li Changzheng; Yan Ying; Li Xiuan — 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target
This oncology nanomedicine paper uses cGAS-STING activation via mtDNA release as a therapeutic mechanism against HCC, offering only a tangential mechanistic parallel without connection to SAMHD1 or the family phenotype.
DOI: 10.1002/adma.75010
Rhapontigenin Alleviates Sepsis-Associated Acute Kidney Injury and Is Accompanied by Modulation of Ferroptosis, Inflammation, and NF-κB Signaling. (from Nephrology/pharmacology)
Kuang Jing; Zhu Xiaoyun; Fang Jun; Hu Shuli; Dai Wei — 2026
Score: 3/10 | Pathways: NF-kB-IKK
This paper studies a plant compound's effect on ferroptosis and NF-κB signaling in sepsis-induced kidney injury, sharing only a peripheral NF-κB mechanism with no connection to SAMHD1, interferonopathy, or mitochondrial dNTP pathways.
DOI: 10.1002/jbt.71096
Single-cell and bulk transcriptomic analyses define an IFI27-centered interferon-response epithelial state in bladder cancer and its transcriptional response to irradiation (from Oncology (bladder cancer radiotherapy))
Yan-Ru Ji; Yang-Yang Zhang; Xiao-Dong Liu; Zhuo-Yuan Lv; Ya-Kai Wang — Frontiers in Cell and Developmental Biology 2026
Score: 3/10 | Pathways: JAK-STAT, ISG15-mitophagy
This paper characterizes an ISG15/IFI27/IFI6-driven interferon-response epithelial state in bladder cancer and its radiation response, sharing downstream ISG/JAK-STAT signaling molecules with the SAMHD1 interferonopathy pathway but with no SAMHD1, cGAS-STING, NLRP3, or mitochondrial mechanistic linkage.
DOI: 10.3389/fcell.2026.1920354
Macrophage immunometabolic reprogramming in inflammatory repair failure in osteonecrosis of the femoral head. (from Orthopedics/bone pathology)
Wang Yan; Zhang LuLu; Liu XueZhi; Wang Dong; Ma JianXiong — 2026
Score: 3/10 | Pathways: NLRP3, other
This paper discusses macrophage immunometabolic reprogramming and NLRP3 inflammasome signaling in osteonecrosis, touching on shared inflammatory pathways but with no direct connection to SAMHD1, interferonopathy, or the family's documented phenotypes.
DOI: 10.1016/j.jot.2026.101212
Mitochondrial extracellular vesicles in cardiorenal syndrome: emerging mediators of mitochondrial signaling and inter-organ crosstalk. (from Nephrology/Cardiology)
Hou Jian; Yang Xiaozhi; Zheng Rui; Li Jianhao; Wang Dayu — 2026
Score: 3/10 | Pathways: VDAC1, other
This review addresses mitochondrial extracellular vesicles in cardiorenal syndrome, sharing only a general mitochondrial dysfunction theme with the SAMHD1 pathway model but no direct mechanistic overlap with cGAS-STING, NLRP3, or SAMHD1-specific biology.
DOI: 10.1080/0886022x.2026.2727298
Clonal Mosaicism of Mitochondrial DNA Heteroplasmy as a Molecular Clock of Aging. (from Aging/genomics biology)
Chang Renin; Tsai Andy P; Wang Boyang; Tsui Kuan-Hao; Pang Cheng-Yoong — 2026
Score: 3/10 | Pathways: POLG-mtDNA, other
Discusses mtDNA heteroplasmy and aging with mention of mtDNA-driven innate immune signaling and inflammaging, but does not address SAMHD1, dNTP pool regulation, or the core interferon-mitochondrial pathways central to this disease profile.
DOI: 10.1111/acel.70718
Mitochondrial homeodynamics in ageing: mechanisms, resilience, and interventions. (from Gerontology/aging biology)
Chmielewski Piotr Paweł — 2026
Score: 3/10 | Pathways: POLG-mtDNA, other
General review of mitochondrial ageing homeodynamics with broad quality-control/mitophagy/retrograde signaling concepts loosely relevant to the mitochondrial-interferon axis but lacks any SAMHD1, cGAS-STING, NLRP3, or dNTP-specific mechanistic content.
DOI: 10.1007/s10522-026-10506-0
The vicious cycle of SASP and inflammaging promotes aging and age-related diseases. (from Geroscience/aging biology)
Liu Qian; Zheng Yulin; Sun Chongkui — 2026
Score: 3/10 | Pathways: NLRP3, other
General review on cellular senescence, SASP, and inflammaging with only tangential overlap to chronic sterile inflammation themes and no direct SAMHD1/interferonopathy/NLRP3-specific mechanistic linkage.
DOI: 10.1038/s42003-026-10826-4
Pathway Coverage This Week¶
treatment-target: 16 papersNLRP3: 11 paperscGAS-STING: 10 papersNF-kB-IKK: 8 papersother: 6 papersclinical-phenotype: 5 papersJAK-STAT: 5 papersmito-ROS-NF-kB: 3 papersVDAC1: 3 papersNF-kB-NLRP3-priming: 2 papersISG15-mitophagy: 2 papersPOLG-mtDNA: 2 papersurate-NLRP3: 1 papersAGS-spectrum: 1 papersIRF7-metabolic: 1 papers