Generated by samhd1_monitor | Model: claude-sonnet-4-6
Summary: 41 papers evaluated | 12 high-relevance (≥7) | 17 medium (5–6) | 12 low (3–4) | 0 scored <3
Added to Zotero automatically
Spotlight on cGAS-STING: role in disease pathogenesis and therapeutic potential. (from Ophthalmology (senior author Liu Zuguo is an ophthalmologist, suggesting ocular surface/corneal innate immunity application))
Yan Dan; Hu Jiaoyue; Liu Zuguo; Ouyang Weijie — 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, JAK-STAT, NLRP3, POLG-mtDNA, treatment-target, AGS-spectrum, ME-CFS
This comprehensive review directly covers the BLUE stream (cGAS→cGAMP→STING→IRF3→IFN-I) that is central to the SAMHD1 A565T mechanism, including mitochondrial/micronuclear DNA sensing, liquid-liquid phase separation dynamics, metabolic-immune crosstalk, neurodegenerative and autoimmune contexts, and emerging small-molecule inhibitors (including cGAS inhibitors like IMSB301-class compounds) that represent direct therapeutic targets for this interferonopathy.
DOI: 10.1186/s43556-026-00478-5
Mitochondria as convergence hubs for innate immunity pathways. (from Cell biology / mitochondrial biology)
Guo Yunhao; Xue Yansong — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, ME-CFS, other
This review directly addresses the convergence of mitochondria as innate immune signaling hubs integrating cGAS-STING, NLRP3, and MAVS pathways through mitochondrial DAMPs—precisely the mechanistic framework (BLUE, PURPLE, RED streams) underlying the SAMHD1 A565T interferonopathy, linking mitochondrial dysfunction to autoimmunity and offering therapeutic pathway insights.
DOI: 10.1038/s42003-026-10479-3
Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis. (from Neurology/Neuroimmunology)
Liu Yongqing; Ye Yingzhi; Fan Minghua; Cheng Henry Yi; Sun Shuying — 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, dNTPase, treatment-target, other
This paper directly demonstrates the mechanistic axis of cytosolic mtDNA release → cGAS-STING → NLRP3 chronic neuroinflammation in microglia, and critically implicates Cmpk2 (a mitochondrial dNTP kinase regulating mtDNA synthesis) as a regulatory node—directly paralleling SAMHD1's role in dNTP pool control and mtDNA-driven innate immune activation in the BLUE and PURPLE pathways, with KAT7 inhibition as a pharmacologically tractable intervention point.
DOI: 10.1016/j.neuron.2026.05.015
A pore is a pore is a pore (or a hub?): VDAC oligomerization in mitochondrial connectivity and modulation. (from Structural biology / mitochondrial biophysics)
De Pinto Vito; Battiato Giuseppe; Conti-Nibali Stefano; Cubisino Salvatore Anton — 2026
Score: 8/10 | Pathways: VDAC1, cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, ISG15-mitophagy
This review directly covers VDAC1 oligomerization, macropore formation, mtDNA escape mechanisms, outer mitochondrial membrane permeabilization, and emerging small-molecule modulators (including VBIT-4 class compounds), all of which are central to the BLUE stream (SAMHD1/VDAC1 interaction loss → VDAC1 macropore → cytosolic mtDNA → cGAS-STING-IRF3-IFN-I) in the disease mechanism, and discusses therapeutic targeting strategies directly applicable to this interferonopathy.
DOI: 10.1042/bst20250480
Mitochondrial kinase CMPK2 in immune homeostasis and disease: from metabolic regulation to inflammatory signaling. (from Biochemistry/Virology)
Junhu Yao; Mengjie Shi; Siyan Chen; Huan Zhang; Yiming Lin — International immunopharmacology 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, dNTPase, ME-CFS, treatment-target, other
CMPK2 is a mitochondrial nucleotide kinase that directly links mitochondrial dNTP pool regulation (UTP/CTP synthesis for mtDNA replication) to both NLRP3 inflammasome activation and cGAS-STING signaling via oxidized/escaped mtDNA, positioning it as a mechanistic neighbor to SAMHD1's dNTPase deficiency cascade, with additional relevance to SARS-CoV-2/post-viral contexts and SLE interferonopathy overlapping the AGS spectrum.
DOI: 10.1016/j.intimp.2026.116582
MitoSafe hypothesis: safeguarding mitochondrial morphology and innate immunity. (from Cell biology / mitochondrial biology)
Nora Haggerty; Kentaro Nakamura; H. Sesaki; M. Iijima — Trends in cell biology 2026
Score: 8/10 | Pathways: cGAS-STING, ISG15-mitophagy, VDAC1, POLG-mtDNA, ME-CFS
This paper directly addresses PINK1/Parkin-mediated mitophagy dysregulation leading to mitochondrial enlargement, mtDNA release, and STING-mediated inflammation — precisely the RED and BLUE pathway loops in the SAMHD1 haploinsufficiency mechanism where ISGylation of MFN1/MFN2 blocks PINK1/Parkin mitophagy, causing damaged mitochondrial accumulation, mtDNA escape, and cGAS-STING activation.
DOI: 10.1016/j.tcb.2026.04.007
Neuroprotection by lactate in Parkinson's disease: A novel anti-inflammatory mechanism via 14-3-3 protein lactylation. (from Neurology/Neurodegeneration (Parkinson's disease))
Zhang Qi; Liu Ming; Cao Wen-Jing; Zou Wei; Zhang Ping — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, other
This paper directly demonstrates the mechanistic triad central to SAMHD1 haploinsufficiency pathology—NLRP3 inflammasome activation, cytosolic mtDNA release, and cGAS-STING pathway engagement—and shows that lactate/14-3-3 lactylation can interrupt this loop at multiple nodes (NLRP3 suppression → reduced GSDMD-driven mitochondrial injury → decreased cytosolic mtDNA → attenuated cGAS-STING), identifying lactate signaling as a novel upstream brake on the BLUE and PURPLE pathway convergence points relevant to the disease mechanism.
DOI: 10.1016/j.bbadis.2026.168314
A Narrative Review of the mtDNA-Stimulated Inflammatory Axis in Sepsis-Induced Acute Lung Injury: Cellular Mechanisms and Therapeutic Targeting. (from Critical care / pulmonology)
Ma Shuqi; Pan Qiusha; Zeng Ruifeng; Liu Quanle; Yang Suyi — 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target, other
This review directly covers the mtDNA-cGAS-STING-NLRP3 inflammatory axis with cell-type-specific mechanistic detail and therapeutic targeting strategies (STING inhibitors, MCC950-class NLRP3 blockers) that map precisely onto the BLUE and PURPLE pathways of SAMHD1 haploinsufficiency, where cytosolic mtDNA escape via VDAC1 macropores drives chronic interferonopathy and pyroptosis, making it highly mechanistically relevant even though SAMHD1 is not mentioned.
DOI: 10.1093/jleuko/qiag077
Small but mighty: mitochondrial DNA at the centre of retrograde signalling (from Cell biology / mitochondrial biology)
Eve Harding; Veronica Bazzani; C. Vascotto — Cell Communication and Signaling : CCS 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, dNTPase, ME-CFS, other
This review directly addresses mtDNA escape, retrograde signalling via cGAS-STING innate immune activation, POLG/mtDNA instability, and mitochondrial dynamics—all core mechanistic streams of the SAMHD1 A565T syndrome—making it highly relevant as a mechanistic framework paper despite lacking direct SAMHD1 data.
DOI: 10.1186/s12964-026-02858-4
Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies (from hepatology/transplant surgery)
Ruotong Shen; Peng An; Meng Chen; Ping Lu; Jingjing Yang — Journal of Translational Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ISG15-mitophagy, treatment-target, other
This paper directly elaborates the mtDNA-release → cGAS-STING → NLRP3 inflammasome → pyroptosis vicious cycle that constitutes the BLUE and PURPLE mechanistic streams of the SAMHD1 haploinsufficiency syndrome, covering VDAC1 permeability, mitophagy failure, and pharmacological intervention points (cGAS-STING and NLRP3 inhibition) directly relevant to therapeutic targeting in the family's interferonopathy.
DOI: 10.1186/s12967-026-08155-5
From symbiosis to immunity: the evolutionary revival of mitochondrial defense programs in inflammatory diseases (from Evolutionary biology / mitochondrial biology)
Weilong Hong; Shiyu Long; M. Ashrafizadeh; Gautam Sethi; Chenyang Duan — Cell Communication and Signaling : CCS 2026
Score: 7/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, ME-CFS, other
This review directly addresses the core convergence of mitochondrial dysfunction, mtDNA release, DAMP-driven innate immune activation (cGAS-STING, NLRP3), and mitophagy failure that constitutes the mechanistic heart of the SAMHD1 A565T interferonopathy model, including VDAC1-mediated mtDNA escape and the progression from mitochondrial stress to systemic inflammatory amplification, though SAMHD1 itself is not mentioned.
DOI: 10.1186/s12964-026-02736-z
Understanding cardiovascular aging as a disorder of mitochondrial network (from Cardiology)
Taslima Akter Shila; Dhrubo Ahmad; Jianli Zhao; Huilan Tan; Bo Wang — The Journal of Cardiovascular Aging 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, ISG15-mitophagy, POLG-mtDNA, NLRP3, treatment-target, clinical-phenotype
This review directly covers mtDNA release activating cGAS-STING, mitophagy/fission-fusion defects, and mitochondrial network dysfunction driving sterile inflammation — all core RED/BLUE/PURPLE stream mechanisms in the SAMHD1 haploinsufficiency model — with cardiovascular aging implications relevant to the family's interferonopathy-cardiac phenotype risk.
DOI: 10.20517/jca.2026.07
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Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles. (from Geroscience/aging biology)
Xiang Zijie; Chen Yu; Liu Xishui; Lu Haowen; Yang Yuqing — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, POLG-mtDNA, mTOR-lysosomal, treatment-target, other
This review systematically covers mitochondrial dysfunction mechanisms directly relevant to the disease model—including cGAS-STING activation by escaped mtDNA, mitophagy failure, mitochondrial dynamics (MFN1/MFN2-related), biogenesis (PGC-1alpha), and mtDNA instability—and surveys therapeutic strategies (including mitochondrial transplantation and base editing) that could apply to SAMHD1 haploinsufficiency's convergent interferon-mitochondrial syndrome, though it does not address SAMHD1 specifically.
DOI: 10.1002/mco2.70790
Intrinsically Mitochondria-Targeting Nanozyme via Coordination-Assembly of Natural Quercetin for Cascade Antioxidant Therapy of Cerebral Ischemia-Reperfusion Injury. (from Nanomedicine/Neurology)
Zheng Wenxuan; Wang Zhicheng; Zhou Xin; Wang Shuya; Shi Xiaojing — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other
This paper directly demonstrates the mtDNA leakage → cGAS-STING neuroinflammatory axis (core BLUE stream) and shows that stabilizing mitochondrial outer membrane proteins (including VDAC1-related outer membrane targets) prevents mtDNA escape, offering mechanistic and therapeutic parallels to the SAMHD1 haploinsufficiency syndrome's central pathogenic loop, though it is framed in cerebral ischemia-reperfusion rather than interferonopathy or SAMHD1 contexts.
DOI: 10.1002/advs.76038
Size-dependent ruthenium/ceria nanozymes synchronize catalytic ROS scavenging and electrostatic mtDNA sequestration for periodontitis therapy. (from Dental/biomaterials nanomedicine)
Zhang Fanrou; Qi Manlin; Liu Jia; Du Juanrui; Shi Fangyu — 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, NLRP3, treatment-target, other
This paper directly addresses the mtDNA escape → cytosolic mtDNA → innate immune activation axis (core BLUE pathway) and mitochondrial oxidative stress, proposing electrostatic sequestration of cytosolic mtDNA as a therapeutic strategy that could conceptually apply to SAMHD1-driven cGAS-STING activation, though it is disease-specific to periodontitis and not mechanistically linked to SAMHD1 or dNTPase dysfunction.
DOI: 10.1186/s12951-026-04660-3
Sex Differences in Mitochondrial Function: Endocrine Regulation, Immunometabolic Signaling, and Implications for Health and Disease. (from Endocrinology/reproductive biology)
Bynum Hanna; Edwards Kristin S — 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, JAK-STAT, ME-CFS, treatment-target, pregnancy-fetal, other
This review directly covers mtDNA release activating cGAS-STING, NLRP3 inflammasome, and mitochondrial quality control pathways central to the SAMHD1 A565T mechanism, and addresses sex-hormone modulation of mitochondrial biogenesis, ROS, and immunometabolic signaling that would modulate disease expression across the multi-generational family, but does not address SAMHD1 specifically or dNTP pool dynamics.
DOI: 10.3390/ijms27114966
No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases (from Mitochondrial disease / clinical genetics)
M. Marchais; Alessandra Pennisi; Alexandre Pierga; A. Lepelley; Nicolas Cagnard — European Journal of Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, POLG-mtDNA, JAK-STAT, ME-CFS, other
This paper directly interrogates the cGAS-STING axis and cytosolic mtDNA leakage in patient fibroblasts with mitochondrial disease, finding that ISG elevation and mtDNA escape are dissociated—a critical negative finding that complicates the BLUE/PURPLE pathway model where VDAC1-mediated mtDNA escape drives IFN-I in SAMHD1 haploinsufficiency, and raises important methodological cautions about using fibroblast models to validate the proposed SAMHD1 A565T interferon-mitochondrial mechanism.
DOI: 10.1002/eji.70176
Advances in Elucidating the Mitochondrial DNA Mechanisms Underlying Ozone-Induced Inflammation (from Environmental toxicology/pulmonology)
Qian Chen; Hao Liu; Junhe Zhou; Yongjie Wei; Lingyan He — Toxics 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, VDAC1, POLG-mtDNA, ME-CFS, other
This review directly addresses mtDNA escape from dysfunctional mitochondria as a DAMP activating innate immune/inflammatory pathways (cGAS-STING, NLRP3), which mirrors the BLUE and PURPLE mechanistic streams of SAMHD1 haploinsufficiency, though the upstream trigger is ozone rather than dNTP pool expansion via SAMHD1 loss.
DOI: 10.3390/toxics14030248
Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects (from Cardiology)
Mingyang Ni; Aijia Zheng; Hang Zheng; Wenqing Jia; Yuansheng Wang — Frontiers in Cardiovascular Medicine 2026
Score: 6/10 | Pathways: POLG-mtDNA, cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, clinical-phenotype, other
This review directly addresses mtDNA mutation-driven innate immune activation (cGAS-STING, NLRP3), mitochondrial structural dysfunction (VDAC1, dynamics), oxidative stress, and metabolic reprogramming in cardiac disease — all core loops of the SAMHD1 interferonopathy mechanism — with cardiology phenotype relevance given the family's interferonopathy-driven mitochondrial cardiomyopathy risk, though SAMHD1 itself is not mentioned.
DOI: 10.3389/fcvm.2026.1781927
Lethal effects of a hyperactive dGTP triphosphohydrolase in E. coli. (from microbiology/biochemistry)
Bhawsinghka Niketa; Glenn Katie F; Klemm Bradley P; Singh Deepa; Day Ryan C — 2026
Score: 5/10 | Pathways: dNTPase, POLG-mtDNA, other
This paper directly investigates the consequences of hyperactive dGTPase activity causing dGTP depletion and chromosomal disruption in E. coli, which is mechanistically inverse but conceptually adjacent to the SAMHD1 haploinsufficiency disease model where reduced dNTPase activity causes dGTP pool expansion — both scenarios underscore the critical importance of precise dNTP pool regulation, particularly dGTP, for genomic integrity and cell viability.
DOI: 10.1093/genetics/iyag139
Mitochondrial Metabolic Reprogramming in Colorectal Cancer-Associated Fibroblasts: An Up-to-Date Review. (from Oncology/Cancer Biology)
Li Ying; Chanda Dipanjan; Jeon Seong-Woo; Jeon Jae-Han; Kim Min-Ji — 2026
Score: 5/10 | Pathways: cGAS-STING, NLRP3, VDAC1, ISG15-mitophagy, mTOR-lysosomal, other
This review covers CAF mitochondrial reprogramming in CRC and explicitly discusses mtDNA-mediated cGAS-STING signaling, AMPK-PGC-1α, mitophagy/fission-fusion dynamics, and ROS-NF-κB pathways that are directly mechanistically relevant to the SAMHD1 interferonopathy model, but the context is tumor-stroma crosstalk rather than germline interferonopathy or dNTPase haploinsufficiency, making the connection indirect.
DOI: 10.3390/cancers18111786
Manganese Vacancy-Engineered Prussian Blue Triggers Pyroptosis-Driven Innate Immunity for Second Near-Infrared Region Photoimmunotherapy. (from Oncology/Nanomedicine)
Wang Xiaorui; Li Runtao; Wang Ye; Li Yunpeng; Liu Liren — 2026
Score: 5/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, other
This paper demonstrates the mechanistic link between ROS-induced gasdermin E-mediated pyroptosis, cytosolic mtDNA release, and cGAS-STING activation—pathways directly relevant to the SAMHD1 disease model—but in an engineered oncology/photoimmunotherapy context that is mechanistically informative but clinically distant from haploinsufficiency-driven interferonopathy.
DOI: 10.1021/acsnano.6c05567
Barrier-to-autointegration factor protects against the cGAS-STING response to chromatin bridges. (from Cell biology / mitosis)
Chastant Laura; Normandin Karine; El-Mortada Firas; Servant Marc J; Archambault * — 2026
Score: 5/10* | Pathways: cGAS-STING, other
This paper characterizes BAF (Barrier-to-Autointegration Factor) as a suppressor of cGAS-STING activation via chromatin bridge stabilization—a nuclear/mitotic mechanism distinct from the SAMHD1/VDAC1/mtDNA route, but confirming that cGAS-STING can be potently activated by aberrant chromatin structures and that IRF3-dependent proinflammatory transcription results; relevant as contextual mechanistic background for the BLUE stream but does not touch SAMHD1, mitochondria, dNTP pools, or any family phenotype directly.
DOI: 10.1371/journal.pgen.1012191
Acacetin ameliorates MASLD by inhibiting the Notch1 pathway in hepatocytes and reprogramming macrophage polarization via Keap1-Nrf2-mediated restraint of ferroptosis. (from Hepatology)
Xu Jun; Ying Huiya; Wang Yixiao; Zeng Yuan; Zhao Qian — 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, IRF7-metabolic, NLRP3, treatment-target, other
The paper directly demonstrates that mitochondrial injury drives mtDNA release activating cGAS-STING in macrophages (a core BLUE-stream pathway in the disease model), and documents hepatic steatosis/MASLD — a tracked family phenotype — but the mechanism is studied in a non-SAMHD1 context with no connection to dNTPase haploinsufficiency, making it an adjacent mechanistic parallel rather than a direct hit.
DOI: 10.1016/j.metabol.2026.156670
Mitochondrial OXPHOS restricts SARS-CoV-2 replication. (from virology/cell metabolism)
Soto Albrecht Yentli E; Morrow Ryan M; Kenney Devin; Olali Arnold Z; Wacquiez Al — 2026
Score: 5/10 | Pathways: POLG-mtDNA, ME-CFS, dNTPase, other
This paper demonstrates that mitochondrial OXPHOS suppresses SARS-CoV-2 replication via metabolic balance rather than innate immune differences, which is indirectly relevant because the SAMHD1 A565T haploinsufficiency causes mitochondrial dysfunction (via POLG stalling, perturbed dNTP pools, and OXPHOS impairment), potentially creating a permissive environment for enhanced SARS-CoV-2 replication and post-viral ME/CFS triggering in the proband, but the paper explicitly rules out innate immune pathway differences as the mechanism, limiting its direct relevance to the cGAS-STING/interferonopathy axis central to this disease.
DOI: 10.1126/sciadv.adz3081
Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion (from Oncology)
Fan Yang; Rui Liu; Li Liu; Aijie Zhang; Bo Li — Frontiers in Immunology 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, other
This review covers cGAS-STING, type I interferon, and innate immune evasion mechanisms directly relevant to the SAMHD1 interferonopathy framework, including metabolic reprogramming and ubiquitin-mediated regulation, but the lung cancer focus and lack of SAMHD1, NLRP3, VDAC1, or mitophagy content limits direct applicability to the disease profile.
DOI: 10.3389/fimmu.2026.1842558
The human cytomegalovirus vMIA protein inhibits apoptosis and innate immune signaling in human Mueller cells. (from ophthalmology/virology)
M. M. Sauter; H. Noel; Curtis R. Brandt — Experimental eye research 2026
Score: 5/10 | Pathways: cGAS-STING, VDAC1, ME-CFS, other
The paper demonstrates viral modulation of the cGAS-STING pathway and mitochondrial apoptosis signaling via vMIA, which intersects with core BLUE-stream mechanisms (cGAS-STING, mitochondrial morphology/MAVS, VDAC1-adjacent apoptosis) relevant to SAMHD1 interferonopathy, but the retinal/ocular context and viral immunoevasion framing are tangential to the family's haploinsufficiency syndrome.
DOI: 10.1016/j.exer.2026.111009
JAK inhibition in PD-1 immunotherapy and tumor microenvironment (from Oncology/Immuno-oncology)
Ziyuan Liu; Jiaqi Liu; Hongyu Chu; Zhuming Lu; Shengshan Xu — Frontiers in Immunology 2026
Score: 5/10 | Pathways: JAK-STAT, treatment-target, other
This review covers JAK/STAT signaling and JAK inhibitors (baricitinib, ruxolitinib class) in the tumor microenvironment, which are directly relevant as treatment targets for the SAMHD1 interferonopathy (IFN-I → JAK-STAT1/2 → ISG15 → mitophagy block), but the paper's focus is on cancer immunotherapy resistance rather than the interferonopathy or mitochondrial mechanisms central to SAMHD1 haploinsufficiency, making it an indirect therapeutic connection.
DOI: 10.3389/fimmu.2026.1790936
Dysregulated dsRNA sensor signaling and viral infection during onset of pediatric autoimmune interferonopathy (from Pediatric rheumatology/myology)
MOREAU, T. R.; AQUINO, Y.; ZHU, Y. Y.; BONDET, V.; ALBERT-VEGA, C.; DONNADIEU, F — bioRxiv (preprint) 2026
Score: 5/10 | Pathways: JAK-STAT, AGS-spectrum, ME-CFS, cGAS-STING, clinical-phenotype, other
This paper demonstrates SARS-CoV-2 and RNA viral triggers driving dysregulated IFN-I/MDA5 signaling with myeloid ISG enrichment in pediatric autoimmune interferonopathy (JDM), which is mechanistically adjacent to the SAMHD1 haploinsufficiency model—particularly the viral trigger hypothesis (proband's adenovirus/SARS-CoV-2 onset), IFN-I loop amplification, and JAK-STAT pathway dysregulation—but does not address SAMHD1, cGAS-STING, VDAC1, mtDNA, or the specific dNTP-driven mechanism.
DOI: 10.64898/2026.05.27.728148
Potential specialty bridges — skim titles
Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases. (from cell biology / molecular pharmacology)
Borlepawar Ankush; Neu Marco; Ma Ziqi; Deshpande Anushka; Bühringer Hannah — 2026
Score: 4/10 | Pathways: mTOR-lysosomal, ISG15-mitophagy, NLRP3, other
This broad proteostasis review tangentially touches autophagy-mitophagy, ubiquitin-proteasome, and lysosomal pathways relevant to the ISG15-mitophagy block and NLRP3 inflammasome axes in the disease model, but contains no specific focus on SAMHD1, cGAS-STING, interferonopathy, or the core molecular players driving the convergent interferon-mitochondrial syndrome.
DOI: 10.1038/s41392-026-02714-4
Association Between Type I Interferonopathies and the Development of Cutaneous Sarcoidosis, Morphea, Lichen Planus and Granuloma Annulare: A Retrospective Cohort Study. (from Dermatology)
Block Brandon; Mehta Jaanvi; Soto-Canetti Gabriela; Tang Alice; Spingler Riley — 2026
Score: 4/10 | Pathways: JAK-STAT, AGS-spectrum, clinical-phenotype, other
This paper documents clinical associations between IFN-I-driven systemic diseases and specific autoimmune dermatoses (LP, morphea, CS, GA), confirming that chronic type I interferonopathy states predispose to these skin conditions, which is peripherally relevant as downstream phenotypic consequences of the same JAK-STAT/IFN-I axis central to SAMHD1 haploinsufficiency, but provides no mechanistic insight into cGAS-STING, NLRP3, VDAC1, or SAMHD1-specific pathways.
DOI: 10.1111/exd.70295
Coexisting ADAR and TSHB Mutations in an Infant With Retinal Detachment and Transient Cardiomyopathy. (from Neonatology/Pediatric Genetics)
Draidi Tamer; Khalil Mohammad; Kabaha Abed; Zuriqi Rafat; Masu'd Mohammad — 2026
Score: 4/10 | Pathways: AGS-spectrum, cGAS-STING, clinical-phenotype
This case documents ADAR-related AGS6, a type I interferonopathy sharing the AGS-spectrum with SAMHD1-related disease, but involves a different gene (ADAR), a distinct molecular mechanism (RNA editing failure rather than dNTPase/cGAS-STING), and the clinical novelty is the co-occurring TSHB mutation; the connection to SAMHD1 haploinsufficiency pathways is only via the broad interferonopathy/AGS diagnostic category.
DOI: 10.1155/crie/5534847
NF-κB signaling in osteoarthritis: integrating mechanical stress, innate immunity, and cartilage degeneration (from Rheumatology/Orthopedics)
Peng Wan; Yimin Zheng — Frontiers in Immunology 2026
Score: 4/10 | Pathways: NLRP3, VDAC1, POLG-mtDNA, urate-NLRP3, other
This OA review touches on NF-κB as a hub integrating mitochondrial dysfunction-associated DNA sensing (obliquely referencing cGAS-STING/NLRP3 pathways) and DAMP-driven innate immune circuits that overlap mechanistically with the SAMHD1 interferonopathy framework, but remains disease-context-specific to cartilage degeneration with no direct relevance to SAMHD1, type I interferon, ISG15-mitophagy, or the family phenotype cluster.
DOI: 10.3389/fimmu.2026.1842443
Identification and diagnostic potential of pyroptosis-related genes in endometriosis: A novel bioinformatics analysis and validation. (from Gynecology/reproductive medicine)
Wang Li; Teng Piaopiao; Chen Jiawen; Ding Caiyun; Luo Xianchen — 2026
Score: 3/10 | Pathways: NLRP3, clinical-phenotype, other
This paper investigates pyroptosis-related genes in endometriosis with some NLRP3/inflammasome relevance and touches on a gynecologic inflammatory condition, but the identified gene signatures (KIF13B, BAG6, MYO5A, HEATR2) have no direct connection to SAMHD1 pathways, cGAS-STING, or the core interferon-mitochondrial mechanism, making this only tangentially relevant via the shared pyroptosis/inflammasome biology and the family's endometrial carcinoma phenotype.
DOI: 10.1371/journal.pone.0350751
A designed peptide disrupting viral protease cleavage restores cGAS-DNA phase separation and type I interferon responses. (from veterinary virology / antiviral therapeutics)
Yin Hongyan; Zhao Zhenchao; Wang Haiwei; Li Xin — 2026
Score: 3/10 | Pathways: cGAS-STING, NLRP3, other
While the paper involves cGAS-DNA phase separation and innate immune signaling (cGAS-STING pathway) relevant to the disease mechanism, the context is entirely viral (SVV 3C protease in porcine systems) and addresses antiviral peptide inhibition rather than constitutive interferonopathy or SAMHD1-related pathology, making the connection tangential at best.
DOI: 10.1371/journal.ppat.1014291
Mechanisms by Which Exercise Delays Brain Aging Through Regulation of the Mitochondrial Quality Control System. (from Exercise physiology / sports medicine / neuroscience)
Zhu Xinyi; Shi Lei; Dong Yahong; Sun Yingjie; Jin Qiguan — 2026
Score: 3/10 | Pathways: mTOR-lysosomal, ISG15-mitophagy, other
This review covers mitochondrial quality control (biogenesis via PGC-1α/AMPK/SIRT1, mitophagy via PINK1/Parkin/mTOR, dynamics via Drp1) which are downstream components of the RED and PURPLE streams, but the paper is entirely focused on exercise as an intervention for brain aging with no connection to SAMHD1, interferonopathy, cGAS-STING, NLRP3, or the specific pathological context of this family.
DOI: 10.3390/biology15110854
The Role of MicroRNAs Carried by Extracellular Vesicles in Tumorigenesis Through Reprogramming the Mitochondrial Information Processing System. (from Oncology/Cancer Biology)
Ghosh-Mitra Arpita; Patel Mansi; Das Samarjit — 2026
Score: 3/10 | Pathways: VDAC1, POLG-mtDNA, mTOR-lysosomal, other
This review covers EV-miRNA reprogramming of mitochondrial dynamics, fission/fusion, and intrinsic apoptosis in tumorigenesis, touching peripherally on mitochondrial dysfunction and immune regulation relevant to the disease mechanism, but does not address SAMHD1, cGAS-STING, NLRP3, ISG15, interferonopathy, or any direct pathway component with meaningful specificity.
DOI: 10.3390/ijms27115112
Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics. (from hepatology-nephrology-cardiology (fibrosis))
Feng Yourong; Zhang Xudong; Wang Xin Joy; Chen Chen — 2026
Score: 3/10 | Pathways: IRF7-metabolic, mTOR-lysosomal, other
This review covers metabolic reprogramming in fibrosis (Warburg effect, glycolysis, lipid metabolism) with some overlap in downstream metabolic consequences of mitochondrial dysfunction and NF-kB/inflammatory signaling, but does not address cGAS-STING, NLRP3, SAMHD1, interferonopathy, or the core pathways driving the A565T syndrome, making the connection tangential.
DOI: 10.1186/s43556-026-00490-9
Clonal lineage tracing of innate immune cells in human cancer. (from Oncology/Tumor Immunology)
Vincent Liu; Katalin D. Sandor; Patrick K. Yan; Zhuang Miao; Yajie Yin — Cancer cell 2026
Score: 3/10 | Pathways: POLG-mtDNA, other
While this paper uses somatic mtDNA mutations as lineage tracing barcodes to study innate immune clonal dynamics in the tumor microenvironment, its use of mtDNA is purely as a neutral genetic marker rather than addressing any mechanistic pathway relevant to SAMHD1 haploinsufficiency, cGAS-STING, NLRP3, or mitochondrial dysfunction in the disease context.
DOI: 10.1016/j.ccell.2026.05.006
Effect of nanobody-STING agonists on the tumor microenvironment and adoptive cell therapy for solid tumors. (from Oncology/Immunotherapy)
Neil C. Chada; Alex Lee; Hailey Jane Frank; Dawn K. Oh; Hannah Ki — Journal of Clinical Oncology 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target, other
This paper involves STING pathway activation but purely in the context of tumor immunotherapy (adoptive cell therapy for solid tumors), with no mechanistic connection to SAMHD1 haploinsufficiency, interferonopathy, mitochondrial dysfunction, or the family phenotype constellation; the STING agonism here is an oncologic tool rather than an exploration of pathological constitutive cGAS-STING activation.
DOI: 10.1200/jco.2026.44.16_suppl.e14601
Abstract LB415: Nanobody:STING agonists reprogram the tumor microenvironment and improve adoptive cell therapy for solid tumors (from Oncology/Immuno-oncology)
Neil C. Chada; Alex Lee; Hailey Jane Frank; Dawn K. Oh; Hannah Ki — Cancer Research 2026
Score: 3/10 | Pathways: cGAS-STING, treatment-target, other
While this paper involves STING pathway activation, it focuses on a nanobody-based tumor immunotherapy platform for solid tumors rather than any aspect of SAMHD1 haploinsufficiency, interferonopathy, or the downstream mitochondrial/inflammasome mechanisms relevant to the disease profile; STING is used here as a pharmacological target to enhance adoptive cell therapy, not in the context of constitutive cGAS-STING activation from mtDNA escape or SAMHD1 dysfunction.
DOI: 10.1158/1538-7445.am2026-lb415
other: 36 paperscGAS-STING: 30 papersNLRP3: 23 papersPOLG-mtDNA: 23 papersVDAC1: 20 paperstreatment-target: 16 papersISG15-mitophagy: 15 papersME-CFS: 12 papersJAK-STAT: 7 papersclinical-phenotype: 6 papersmTOR-lysosomal: 6 papersdNTPase: 5 papersAGS-spectrum: 4 papersIRF7-metabolic: 3 paperspregnancy-fetal: 1 papersurate-NLRP3: 1 papers