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September 2026

Emerging microbiome–mitochondria crosstalk in host defense and infectious diseases: mechanistic insights into NLRP3 inflammasome activation and mtDNA-mediated immunomodulation

The finding

This review synthesizes recent evidence that gut microbiota metabolites—short-chain fatty acids, trimethylamine, and indole derivatives—directly modulate mitochondrial function and reactive oxygen species (ROS) production, which in turn gates NLRP3 inflammasome activation. The authors also consolidate findings that dysbiosis promotes mitochondrial stress and mtDNA release, with mtDNA acting as a damage-associated molecular pattern that can engage both cGAS-STING and NLRP3 signaling, linking gut microbial shifts to systemic inflammation across colitis, neurodegeneration, and sepsis.

Where it fits

This review speaks directly to Loop B (mitochondrial/NLRP3) and provides a critical checkpoint insight relevant to SAMHD1 A565T. The paper's central claim—that mitochondrial ROS and mtDNA fragmentation are upstream licensing events for NLRP3—mirrors the model's proposed mechanism whereby POLG replisome stress generates oxidized mtDNA (8-OHdG) that primes NLRP3 rather than cGAS. The review's emphasis on PINK1/Parkin-mediated mitophagy as a brake on this pathway is directly relevant: in the SAMHD1 model, ISG15 ISGylates MFN1/2 and BECN1 to block mitophagy, creating a self-sustaining loop. The review also reinforces the dual-sensor logic—mtDNA can hit both cGAS-STING and NLRP3 via distinct routes—which is the model's central testable claim. Finally, the microbiome–mitochondria axis suggests an environmental modifier: gut-derived metabolites could tune the threshold for NLRP3 licensing in SAMHD1 carriers, potentially explaining variable penetrance.

Caveats

  • This is a review, not primary data; the mechanistic links are synthesized from disparate studies, often in different cell types or disease models.
  • The microbiome–mitochondria–NLRP3 connections are largely demonstrated in non-SAMHD1 contexts (colitis, sepsis); extrapolation to SAMHD1 A565T is inferred, not tested.
  • The review does not address heterozygous vs. homozygous loss-of-function, nor does it quantify how much mitochondrial stress is needed to cross the NLRP3 activation threshold.

What to watch

Does modulating the gut microbiome—via probiotics or metabolite supplementation—alter NLRP3-dependent IL-18/IL-1β output in SAMHD1 models? If so, the microbiome becomes a druggable upstream node for Loop B, potentially complementing JAK inhibition that targets Loop A.

Source: Emerging microbiome–mitochondria crosstalk in host defense and infectious diseases: mechanistic insights into NLRP3 inflammasome activation and mtDNA-mediated immunomodulation — Frontiers in Cellular and Infection Microbiology 2026.

Engineered Exosome-Mediated FIH-1 Delivery for Targeted Therapy of Hyperuricemic Nephropathy by Inhibiting NF-κB/NLRP3 Inflammasome Signaling and Restoring Autophagic Homeostasis

The finding

This paper demonstrates that engineered extracellular vesicles derived from iPSC-MSCs, loaded with FIH-1 (factor inhibiting HIF-1) and decorated with kidney-targeting peptides, suppress uric acid-induced renal tubular epithelial fibrosis. The mechanism involves inhibition of NF-κB/NLRP3 inflammasome signaling and restoration of dysregulated autophagy, validated in both in vitro and in vivo models of hyperuricemic nephropathy.

Where it fits

This work speaks directly to Loop B (mitochondrial & nucleotide-NLRP3) and the purine catabolite arm of the SAMHD1 A565T model — specifically the uric acid-driven priming step. In the 3D causal model, excess dGTP from SAMHD1 dysfunction is catabolized to uric acid (MSU crystals), which acts as a priming signal for NLRP3 via NF-κB. This paper provides independent evidence that uric acid itself can drive NF-κB-dependent NLRP3 priming in renal tubular cells — the same "primed again" step described in Loop B's self-sustaining cycle.

The FIH-1 angle is particularly interesting for the SAMHD1 model. FIH-1 is an oxygen sensor that hydroxylates HIF-1α, but it also modulates NF-κB signaling. The paper shows that restoring FIH-1 suppresses the NF-κB/NLRP3 axis — suggesting FIH-1 acts as a brake on this priming loop. In the SAMHD1 context, this raises the question of whether FIH-1 activity is compromised when dNTP pools expand, or whether FIH-1 restoration could serve as a second independent rescue point alongside JAK inhibition (Loop A) and cGAS blockade.

The autophagy restoration component also connects to the model's mitophagy node: the model posits that ISG15 ISGylates BECN1 and MFN1/2, blocking mitophagy and allowing damaged mitochondria to persist. This paper's finding that FIH-1 restores autophagic homeostasis suggests a potential intersection — if FIH-1 can unblock autophagy, it might also relieve the mitophagy blockade that sustains Loop A.

Caveats

  • This is a hyperuricemic nephropathy model, not a SAMHD1 A565T system — the uric acid source is exogenous, not derived from dNTP catabolism.
  • The study uses FIH-1 overexpression via engineered vesicles, not genetic manipulation of SAMHD1 or its downstream effectors.
  • The NF-κB/NLRP3 link is demonstrated in renal tubular epithelial cells, not in the immune responder cells (NK/Th1/M1 macrophages) that drive Loop C.

What to watch

Whether FIH-1 modulation affects the cGAS-STING arm (Loop A) or only the NLRP3 arm — if FIH-1 delivery suppresses both, it could represent a single-node intervention that breaks the model's central claim of two independent rescue points.

Source: Engineered Exosome-Mediated FIH-1 Delivery for Targeted Therapy of Hyperuricemic Nephropathy by Inhibiting NF-κB/NLRP3 Inflammasome Signaling and Restoring Autophagic Homeostasis — 2026.

HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway

The finding

This paper shows that the HTLV-1 Tax protein hijacks the PINK1–Parkin mitophagy pathway to clear damaged mitochondria and suppress cGAS–STING activation. Tax induces mitochondrial ROS and membrane-potential disruption, then recruits the autophagy receptors CALCOCO2/NDP52 and SQSTM1/p62 to drive mitophagic clearance. Critically, Tax requires PRKN to limit cGAS-STING1 activation and type I interferon induction — a viral immune-evasion strategy that also sustains viral gene expression and cell survival.

Where it fits

This speaks directly to Loop A (IFN-I/JAK-STAT) and the mitochondrial quality-control node that the SAMHD1 A565T model predicts is corrupted. In the SAMHD1 model, ISG15 ISGylates MFN1/2 and BECN1, blocking mitophagy so damaged mitochondria persist and keep leaking mtDNA to cGAS-STING. This paper provides the mechanistic counterexample: when PINK1-Parkin mitophagy works, it clears damaged mitochondria and prevents cGAS-STING activation. That is exactly the clearance step the SAMHD1 model predicts is disabled — and it confirms that mitophagy is a genuine checkpoint for tonic IFN-I, not just a downstream consequence of mitochondrial stress.

The paper also reinforces the model's claim that mtDNA release is the key ligand for cGAS: Tax's suppression of IFN depends on removing the mitochondria that would otherwise release mtDNA, not on directly inhibiting cGAS itself.

Caveats

  • This is a viral system (HTLV-1 Tax), not a SAMHD1 model — the relevance is mechanistic analogy, not direct demonstration in A565T cells.
  • The experiments use overexpression and viral-transformed cell lines, not primary cells from SAMHD1 patients; the mitophagy-cGAS link is established here, but the specific failure mode in A565T remains inferred.
  • The paper shows Tax requires PRKN to suppress cGAS-STING, but does not address whether partial loss of mitophagy (as predicted in SAMHD1 A565T) produces a graded, smouldering IFN response versus an all-or-nothing switch.

What to watch

Does restoring PINK1-Parkin activity in SAMHD1 A565T cells — for example, by blocking ISG15-mediated inhibition of mitophagy — phenocopy Tax's suppression of cGAS-STING? That would be the direct test of whether the model's Loop A is truly self-sustaining via mitophagy blockade.

Source: HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway — 2026.

Modeling calcific aortic valve disease with engineered human valve tissues identifies SAMHD1 as a therapeutic target

The finding

This paper reports the first engineered valvular tissues (EVTs) built from human iPSC-derived valvular interstitial cells in a 3D fibrinogen/Matrigel/collagen I hydrogel, assembled with hiPSC-derived cardiomyocytes to create a self-contracting, mechanically loaded valve model. Using time-series transcriptomics and WGCNA, the authors identify SAMHD1 as a core regulator of calcification, and show that recombinant SAMHD1 protein reduces calcification, restores tissue elasticity, and attenuates dysfunction under both static and cyclic mechanical stress.

Where it fits

This speaks directly to the mitochondrial/NLRP3 arm (Loop B) of the SAMHD1 p.A565T model — and, by extension, to the systemic vascular spectrum of SAMHD1 dysfunction. The paper demonstrates that SAMHD1 acts as a gatekeeper in valve calcification via an inflammatory pathway, which is consistent with the model's claim that reduced SAMHD1 function permits chronic innate-immune tone. The engineered myocardium-valve composite is particularly relevant: it validates that mechanical stress exacerbates calcification, a finding that maps onto the model's Loop C (paracrine/NF-κB/IFN-γ feedback), where tissue-scale mechanical and inflammatory signals converge. For the A565T variant specifically, this raises the possibility that partial loss of SAMHD1 function — sufficient to avoid Aicardi-Goutières syndrome but not to hold the system down — could contribute to a smoldering, non-acute inflammatory state in vascular tissues, with calcification as a downstream clinical outcome. The identification of SAMHD1 as a therapeutic target (rather than just a disease gene) aligns with the model's central claim that the loops are parallel and independently druggable.

Caveats

  • This is a wild-type SAMHD1 study in engineered tissues, not a study of the p.A565T heterozygous variant; the relevance to the specific hypomorphic allele is inferred, not demonstrated.
  • The model uses hiPSC-derived VICs, not primary patient cells, and the "inflammatory signal pathway" is identified via WGCNA correlation plus small-molecule inhibition — association, not direct mechanistic proof of SAMHD1's enzymatic role.
  • Recombinant SAMHD1 protein was added exogenously; the paper does not show whether this rescues via dNTPase activity, protein-protein interactions, or an off-target effect.

What to watch

Does recombinant SAMHD1 rescue calcification in the A565T heterozygous background, and does that rescue track with normalization of dNTP pools and NLRP3 licensing? If so, this engineered tissue platform could become the first scalable, mechanically active assay for screening SAMHD1-rescue therapies across the vascular spectrum.

Source: Modeling calcific aortic valve disease with engineered human valve tissues identifies SAMHD1 as a therapeutic target — 2026.

Structural and single-molecule insights into the core human mitochondrial DNA replisome

The finding

This review integrates recent cryo-EM and single-molecule studies to build a quantitative mechanistic framework for how the core human mitochondrial replisome—POLG, Twinkle, and mtSSB—coordinates replication of the light and heavy strands of mtDNA. The authors synthesize structural data on replisome architecture with dynamic measurements of fork progression, describing how initiation, elongation, and regulation are achieved at the mitochondrial replication fork, and identify remaining gaps toward a complete mechanistic model.

Where it fits

This paper speaks directly to Loop B (Mitochondrial/NLRP3) in the SAMHD1 A565T model—specifically, the proposed mechanism by which dNTP pool expansion causes POLG replisome stress. The model posits that excess cytosolic dNTPs flood mitochondrial carriers, perturb the matrix pool, and stall POLG, leading to oxidized mtDNA (8-OHdG) and VDAC1 destabilization, which licenses the NLRP3 inflammasome. This review provides the structural and kinetic context for why POLG is vulnerable to nucleotide imbalances: the replisome must coordinate leading- and lagging-strand synthesis with a tightly regulated dNTP supply, and asymmetric pools—exactly what a partial loss-of-function SAMHD1 variant would produce—could plausibly stall the polymerase and generate the replication stress that feeds the downstream inflammatory cascade. The single-molecule approaches highlighted here are particularly relevant, as they can directly probe how POLG kinetics respond to altered dNTP concentrations and ratios.

Caveats

  • This is a review, not a primary study; the mechanistic claims are synthesized from other groups' work, not newly demonstrated here.
  • The paper does not address SAMHD1 or any disease variant—it describes the wild-type replisome under normal conditions, not the perturbed state induced by dNTP pool expansion.
  • Structural and single-molecule data come from reconstituted in vitro systems, which may not fully capture the mitochondrial environment (e.g., membrane tethering, local nucleotide compartmentalization) relevant to the A565T pathology.

What to watch

The next key question is whether single-molecule POLG assays can be run under asymmetric dNTP pools mimicking the SAMHD1 A565T state—if POLG stalling is directly observable under those conditions, it would provide a mechanistic bridge from the enzyme defect to the oxidized mtDNA that primes NLRP3.

Source: Structural and single-molecule insights into the core human mitochondrial DNA replisome — 2026.

The consequences of mitochondrial dysfunction and upregulated glycolysis on innate and adaptive immune responses

The finding

This 2026 review by Fabrizio Marcucci and Cristiano Rumio synthesizes how mitochondrial dysfunction and compensatory fermentative glycolysis (the Warburg shift) operate as a dual-edged regulatory axis in immunity. When oxidative phosphorylation (OXPHOS) collapses, the cell upregulates fermentative glycolysis as an emergency "necrosis defense" to maintain basic ATP levels and prevent catastrophic membrane rupture with uncontrolled DAMP release. Simultaneously, the review maps how non-canonical "moonlighting" functions of glycolytic enzymes and overflow metabolites orchestrate contradictory immune fates: pro-inflammatory amplification via PKM2–HIF-1α transcription of IL-1β and NLRP3/AIM2 assembly, juxtaposed against profound epigenetic and post-translational immunosuppression mediated by histone lactylation (e.g., H3K18la) and pyruvate-driven STAT1 Lys201 pyruvilation.

Where it fits

This synthesis sits squarely across the interface between Loop B (Mitochondrial / NLRP3 Inflammasome) and Loop A (Type I Interferon / JAK-STAT) in the SAMHD1 p.A565T architecture:

  1. The Emergency Necrosis Defense (Loop B): In the SAMHD1 framework, mitochondrial nucleotide overload (PNC1/2) and POLG stalling collapse membrane potential (ΔΨm). Marcucci & Rumio explain why this does not immediately trigger fulminant cell lysis: compensatory aerobic glycolysis generates just enough ATP to hold off bioenergetic necrosis (inhibiting MLKL-driven rupture). However, the trade-off is massive intracellular accumulation of pyruvate and lactic acid.
  2. Selective Antiviral Uncoupling via STAT1 Pyruvilation: The authors highlight the emerging discovery (Zuo et al., Cell 2026) that glycolytic pyruvate overflow covalently modifies STAT1 at Lys201. This sterically blocks STAT1–STAT2 heterodimerization (ISGF3), selectively turning down antiviral ISG transcription while leaving NF-κB, STAT3, and IFN-γ/GAF signaling fully intact. This directly resolves a core paradox in the A565T phenotype: heightened viral vulnerability coexisting with unremitting autoinflammatory drive.
  3. The Epigenetic Lactylation Lock & Multi-Day PEM: Excess lactate drives H3K18la histone modifications and synovial T-cell entrapment. While initially protective against runaway inflammation, persistent lactylation locks macrophages into a refractory, exhausted state—providing a compelling mechanistic basis for prolonged post-exertional malaise (PEM) and refractory fatigue.

Caveats

  • Review Synthesis, Not Primary Genetics: The paper aggregates findings across oncology, toxicology (e.g., metformin, tigecycline), and infection models; it does not measure primary cells with heterozygous SAMHD1 mutations.
  • Dose & Microenvironment Dependency: As the authors emphasize, the immunomodulatory polarity of lactate (inflammatory vs. immunosuppressive) is highly sensitive to local extracellular pH, cell-type transporter expression (MCTs), and acute vs. chronic duration.
  • Stoichiometry of PTMs: The physiological abundance of Lys201 pyruvilation relative to standard phosphorylation (p-Y701) in non-transformed human immune cells remains to be quantitatively benchmarked via targeted mass spectrometry.

What to watch

The key translational question is whether pharmacological modulation of mitochondrial substrate influx (e.g., inner-membrane PNC1/2 carriers) or lactic acid dynamics can release the refractory H3K18la chromatin lock and normalize antiviral ISGF3 assembly without compromising the glycolytic energy buffer that protects cells from necrotic collapse.

Source: The consequences of mitochondrial dysfunction and upregulated glycolysis on innate and adaptive immune responses — Cell Signaling, Inflammation & Disease 2026.

The mitochondrial DNA signal in rheumatoid arthritis: From metabolic victim to inflammatory driver

The finding

This 2026 review by Zhang et al. synthesizes evidence that mitochondrial DNA (mtDNA) is not merely collateral damage in rheumatoid arthritis (RA) but an active driver of innate immune signaling. The authors frame the field around a "mtDNA damage–release–immune activation axis": oxidative injury to mtDNA (due to limited chromatin protection and constrained repair) leads to its translocation to the cytosol or extracellular space, where it acts as an immunostimulatory danger signal. They also note that circulating cell-free mtDNA correlates with disease activity and therapeutic response, positioning it as a dynamic clinical biomarker.

Where it fits

This review speaks directly to the convergence point of Loop A and Loop B in the SAMHD1 p.A565T model — the mitochondrion as the organelle where the two chemically distinct DNA species diverge. The paper's central claim — that oxidized mtDNA is the immunostimulatory species — maps precisely onto the model's distinction: unoxidized mtDNA fragments exit via VDAC1 macropores to activate cGAS–STING (Loop A, IFN-I/JAK-STAT), while oxidized mtDNA (8-OHdG) primes NLRP3 (Loop B, mitochondrial/NLRP3). The review's emphasis on impaired mitochondrial quality control also resonates with the model's ISG15-mediated blockade of mitophagy via MFN1/2 and BECN1 — a mechanism that would keep damaged mitochondria leaking. For SAMHD1 A565T, where POLG replisome stress from dNTP pool expansion generates oxidized mtDNA, this framework reinforces the hypothesis that the same molecular species can feed two parallel inflammatory loops — and that targeting mtDNA release or sensing could be a dual-pronged therapeutic strategy.

Caveats

  • This is a review, not primary data — it synthesizes existing findings rather than presenting new mechanistic experiments.
  • The context is rheumatoid arthritis, not SAMHD1 A565T interferonopathy; the relevance to the model is analogical, not direct.
  • The review discusses mtDNA as a biomarker and driver in RA, but does not establish causal directionality in human disease, nor does it address heterozygous partial loss-of-function scenarios.

What to watch

The key translational question: does blocking oxidized mtDNA sensing (e.g., via NLRP3 inhibition) also suppress the cGAS-STING ISG signature in SAMHD1 A565T models — or are the loops sufficiently independent that dual blockade is required? The review's biomarker angle also raises a practical next step: whether circulating cell-free mtDNA could track disease activity in A565T carriers.

Source: The mitochondrial DNA signal in rheumatoid arthritis: From metabolic victim to inflammatory driver — 2026.

Type I Interferonopathies in the Differential Diagnosis of Vasculitis: A Comprehensive Review

The finding

This review positions type I interferonopathies—including SAMHD1-associated disease—as a critical diagnostic consideration in patients presenting with vasculitis, particularly when conventional vasculitis workups are unrevealing. The authors provide a clinical framework for recognizing interferonopathy-driven vascular pathology, emphasizing that intracranial aneurysms and cerebrovascular disease can be the presenting feature of underlying innate immune dysregulation rather than classic autoimmune vasculitis.

Where it fits

This paper speaks directly to the clinical outcome layer of the SAMHD1 A565T model—specifically the vascular complications that emerge from chronic type I interferon tone. In the 3D causal model, this maps to the downstream consequences of Loop A (cGAS → STING → IRF3 → IFN-I → JAK-STAT signaling), where tonic interferon production drives ISG expression and vascular remodeling.

The review's emphasis on interferon score monitoring as a diagnostic tool is particularly relevant for the A565T model. Because the heterozygous variant produces a "non-acute chronic inflammation" (NACI) phenotype rather than fulminant Aicardi-Goutières syndrome, interferon scores may be moderately elevated—enough to flag the diagnosis but not enough to trigger the classic interferonopathy workup. The paper's message that vasculitis can be the presenting feature of these conditions supports the model's claim that SAMHD1 disease is multi-system, with vascular outcomes emerging from chronic, low-amplitude innate immune activation.

For clinicians managing A565T patients, this review reinforces that intracranial aneurysm screening should be part of routine surveillance, and that JAK inhibitor responsiveness (a key feature of Loop A) may offer a therapeutic window for vascular protection.

Caveats

  • This is a review article, not a primary study—it synthesizes existing case reports and series rather than presenting new mechanistic data.
  • The review covers type I interferonopathies broadly; findings may not be specific to SAMHD1 p.A565T, which has a distinct heterozygous, partial-loss-of-function profile.
  • No data on whether interferon score thresholds distinguish A565T vasculopathy from other interferonopathies or from classic vasculitis.

What to watch

Whether longitudinal interferon score monitoring can predict aneurysm formation or progression in A565T carriers—and whether early JAK inhibitor intervention alters vascular outcomes.

Source: Type I Interferonopathies in the Differential Diagnosis of Vasculitis: A Comprehensive Review — Journal of Visualized Experiments 2026.

SAMHD1 Research Digest — 2026-08-19

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 13 papers evaluated | 2 high-relevance (≥7) | 8 medium (5–6) | 3 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

A genome-wide map of the genetic network in monocytes that regulates type I interferon induction by the cGAS-STING pathway. (from functional genomics/CRISPR screening)
Thomsen Emil Aagaard; Zhao Jian; Narita Ryo; Davis Luther J; Olagnier David — Science signaling 2026
Score: 7/10 | Pathways: cGAS-STING, treatment-target, NF-kB-IKK

This CRISPR screen maps genetic regulators of cGAS-STING-driven IFNB1 induction in monocytes, directly relevant to the BLUE pathway (cGAS-STING-IRF3-IFN-I) implicated in SAMHD1 haploinsufficiency and identifies novel druggable nodes (e.g., TBK1/HDAC3) for interferonopathy therapy.
DOI: 10.1126/scisignal.adx3808

Type I Interferonopathies in the Differential Diagnosis of Vasculitis: A Comprehensive Review. (from Rheumatology/vasculitis)
Gürbüz Nida; Ismayilova Shams; Ahmadova Gulnar; Çiftçi Rena; Aksu Güzide — Journal of visualized experiments : JoVE 2026
Score: 7/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, treatment-target, clinical-phenotype

This review directly covers SAMHD1 as a monogenic type I interferonopathy gene within the cGAS-STING/JAK-STAT axis, discusses interferon gene signature diagnostics and JAK inhibitor therapy, and links IFN-I dysregulation to vasculitic/autoimmune phenotypes relevant to the family's rheumatologic and autoimmune manifestations, though it does not focus specifically on SAMHD1 A565T.
DOI: 10.3791/71286

🟡 Medium Relevance (Score 5–6)

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

Atractylodes macrocephala Koidz. Polysaccharides Alleviate Liver Fibrosis in Association With Suppression of cGAS-STING Signaling and Mitochondrial Apoptosis. (from Hepatology/ethnopharmacology)
Wu Jiali; Hu Xianzhe; Liu Jing; Peng Hongye; Chen Bo — Journal of ethnopharmacology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, treatment-target

Demonstrates a natural compound suppressing cGAS-STING-NLRP3 signaling and mitochondrial danger signaling to reduce liver fibrosis, directly relevant to the BLUE/Loop A axis and NF-κB-NLRP3 priming mechanism central to the disease model, though it is in a non-SAMHD1 liver fibrosis context.
DOI: 10.1016/j.jep.2026.122313

The mitophagy-inflammasome axis: a shared pathological hub in Alzheimer's and Parkinson's diseases. (from neurology/neurodegeneration)
Long Wei; Yuan Mengqin; Wang Sirui; Tan Xinyue; Gao Li-Chen — Translational neurodegeneration 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

Reviews mitophagy-inflammasome crosstalk (ROS/mtDNA-driven NLRP3 activation and mitophagy suppression) that parallels the PURPLE/RED/Loop B mechanisms in the SAMHD1 syndrome, though focused on neurodegeneration rather than SAMHD1 directly.
DOI: 10.1186/s40035-026-00578-w

PPARα deficiency exacerbates atherosclerosis progressing through enhancing pTh17 cells-macrophage crosstalk. (from Cardiology/vascular immunology)
Ren Tong; Jiang Xilin; Wu Jianfeng; Yan Changsheng; Peng Lu — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

Demonstrates mtDNA leakage activating the cGAS-STING axis to drive pathogenic immune cell differentiation and inflammation in atherosclerosis, mechanistically parallel to the BLUE loop mitochondrial-to-cGAS-STING signaling in SAMHD1 haploinsufficiency though in a distinct disease context.
DOI: 10.1016/j.ejphar.2026.179247

Long-chain chlorinated paraffins exposure induces premature ovarian failure by disrupting the balance of mitochondrial fission. (from Reproductive toxicology/gynecology)
Xu Chenhui; Deng Haochu; Tian Xue; Ma Shuang; Kong Yuebing — 2026
Score: 6/10 | Pathways: cGAS-STING, other

Demonstrates a toxicant-induced mitochondrial fission-mtDNA leakage-cGAS-STING-senescence axis mechanistically analogous to the disease's BLUE pathway (VDAC1/mtDNA/cGAS-STING) though in a reproductive rather than immune context.
DOI: 10.1007/s11010-026-05696-7

Minimally invasive extracorporeal circulation protects against postoperative pulmonary endothelial injury in elderly cardiac surgery via suppressing the C5a-mtDNA-cGAS-STING axis: a mechanistic randomized controlled trial. (from Cardiothoracic surgery / perioperative critical care)
Zhao Yun; Wang Jiaxing; Yang Zhaohua; Ma Wenrui; Wang Chunsheng — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, other

Demonstrates mtDNA release triggering cGAS-STING activation and endothelial injury in a surgical inflammation model, mechanistically parallel to the BLUE/mitochondrial-cGAS-STING axis in SAMHD1 haploinsufficiency though not disease-specific.
DOI: 10.1016/j.intimp.2026.117281

Engineered Exosome-Mediated FIH-1 Delivery for Targeted Therapy of Hyperuricemic Nephropathy by Inhibiting NF-κB/NLRP3 Inflammasome Signaling and Restoring Autophagic Homeostasis. (from Nephrology/regenerative medicine (exosome-based nanotherapeutics))
Xiao Ting; Liu Yu; He Zhe; Yang Ailing; Li Jing — Advanced healthcare materials 2026
Score: 6/10 | Pathways: urate-NLRP3, NF-kB-NLRP3-priming, NLRP3, treatment-target, mTOR-lysosomal

Demonstrates uric acid/MSU-driven NF-κB/NLRP3 activation and autophagy restoration in nephropathy, directly paralleling the GOLD gout/urate-NLRP3 axis and NF-κB priming crosstalk relevant to SAMHD1-driven interferon-mitochondrial disease, though it is a nephrology/regenerative-medicine context without SAMHD1 linkage.
DOI: 10.1002/adhm.71602

Mitochondrial Dysfunction as a Central Hub of Aging: From Molecular Cascades to Inter-Organ Communication Networks. (from Gerontology/aging biology)
Han Chaodong; Zhang Zilian; Song Yafeng — Gerontology 2026
Score: 5/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target

This general aging review covers cGAS-STING/NLRP3-driven inflammation from mitochondrial dysfunction and mitokine signaling, mechanistically overlapping with the Purple/Blue/Gold loops but without any SAMHD1, dNTP, or disease-specific data.
DOI: 10.1159/000553430

Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells. (from gene therapy / synthetic biology engineering)
Jung Hyuncheol; Devant Pascal; Ching Carter; Ota Mineto; Dann Emma — Nature biotechnology 2026
Score: 5/10 | Pathways: gene-therapy-delivery, treatment-target

This paper describes a VLP-based CRISPR/base-editing delivery platform for primary human myeloid cells, relevant as a potential future correction/delivery strategy for SAMHD1 immune-cell mutations but not directly addressing SAMHD1 or its interferon-mitochondrial mechanism.
DOI: 10.1038/s41587-026-03258-2

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Lactate oxidase-engineered manganese layered double hydroxide nanoplatform amplifies cGAS-STING activation for tumor immunotherapy. (from Nanomedicine/oncology)
Cai Feng; Jiang Dengsheng; Geng Mingzhe; Xu Hongbo; Song Shilong — 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target

Describes cGAS-STING activation via mtDNA release and oxidative mitochondrial damage in a tumor immunotherapy nanoplatform, mechanistically touching the pathway but in an oncology-engineering context unrelated to SAMHD1 haploinsufficiency or its downstream family phenotypes.
DOI: 10.1016/j.ijbiomac.2026.153862

Astragaloside IV Protects against PM2.5-Induced Spermatocyte Injury via the cGAS-STING/Nrf2/HMOX1 Axis. (from reproductive toxicology/andrology)
Jin Jin; Zhang Congxue — Reproductive toxicology (Elmsford, N.Y.) 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target

This paper demonstrates cGAS-STING pathway activation and pharmacologic suppression (via AS-IV) in a PM2.5-induced spermatocyte toxicity model, showing mechanistic overlap with the interferon arm of the syndrome but in an unrelated reproductive toxicology context without SAMHD1 or mitochondrial dNTP linkage.
DOI: 10.1016/j.reprotox.2026.109328

Sex-sikpecific associations between serum uric acid and chronic rhinosinusitis: a retrospective case-control study. (from Otolaryngology/Rheumatology (uric acid metabolism))
Zhou Jiaxin; Wu Fan; Wang Chang; Kong Haobo; Liu Yehai — Frontiers in allergy 2026
Score: 3/10 | Pathways: urate-NLRP3

Paper links serum uric acid to chronic rhinosinusitis via sex-specific effects, touching the GOLD pathway (uric acid/MSU-NLRP3 axis) only tangentially without any SAMHD1, interferon, or mitochondrial mechanism.
DOI: 10.3389/falgy.2026.1870468

Pathway Coverage This Week

  • treatment-target: 11 papers
  • cGAS-STING: 9 papers
  • NLRP3: 4 papers
  • other: 3 papers
  • mito-ROS-NF-kB: 2 papers
  • urate-NLRP3: 2 papers
  • NF-kB-IKK: 1 papers
  • JAK-STAT: 1 papers
  • AGS-spectrum: 1 papers
  • clinical-phenotype: 1 papers
  • NF-kB-NLRP3-priming: 1 papers
  • mTOR-lysosomal: 1 papers
  • gene-therapy-delivery: 1 papers

SAMHD1 Research Digest — 2026-08-16

Generated by samhd1_monitor | Model: claude-sonnet-5

Summary: 29 papers evaluated | 2 high-relevance (≥7) | 14 medium (5–6) | 13 low (3–4) | 0 scored <3

🔴 High Relevance (Score 7–10)

Auto-added to Zotero (threshold ≥6)

Simulated Microgravity Induced Mesenchymal Stem Cell Senescence via the Activation of Cytosolic mtDNA-cGAS-STING Axis. (from Aerospace/regenerative medicine (stem cell biology under microgravity))
Huang Lei; Huang Rui; Lv Wenjun; Li Zimeng; Tu Yun — 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, treatment-target

This paper directly demonstrates the BAK/BAX-VDAC-mediated mtDNA leakage → cGAS-STING activation axis (BLUE stream) driving cellular senescence, mechanistically paralleling the core interferon-mitochondrial pathway implicated in the SAMHD1 A565T syndrome, with STING inhibition (C176) shown as a viable therapeutic strategy.
DOI: 10.1002/jcp.70220

Taulipro rescues mitochondrial dysfunction and inhibits cGAS–STING neuroinflammation in Aβ-driven Alzheimer's disease models (from Neurology/Neurodegeneration (Alzheimer's disease))
Tian Mao; Zhu Xiuping; Lei Zhifeng; Lu Yongheng; Mo Lin — 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, NF-kB-IKK, treatment-target

This paper demonstrates mtDNA leakage-driven cGAS-STING-TBK1-IRF3-NFκB neuroinflammation as an upstream pathogenic mechanism directly analogous to the BLUE/RED loops in the SAMHD1 interferon-mitochondrial syndrome, with a novel therapeutic (Taulipro) targeting the mtDNA leakage step relevant to future treatment strategies.
DOI: 10.21203/rs.3.rs-10416296/v1

🟡 Medium Relevance (Score 5–6)

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

Honokiol targets cyclophilin D and blocks mitochondrial DNA release to inhibit microglial NLRP3 inflammasome activation and alleviate neurodegeneration in Parkinson's disease models. (from Neurology/neurodegeneration (Parkinson's disease) and natural product pharmacology)
Gan Qinglin; Xian Yingtong; Zhou Ting; Fu Xiaolong; Gou Shiyi — Chemico-biological interactions 2026
Score: 6/10 | Pathways: NLRP3, mito-ROS-NF-kB, treatment-target

This paper demonstrates mtDNA release triggering NLRP3 inflammasome activation via mitochondrial permeability transition (CypD), mechanistically parallel to the VDAC1/mtDNA-NLRP3 axis central to the SAMHD1 syndrome, and offers a small-molecule therapeutic (honokiol) strategy relevant to inflammasome modulation.
DOI: 10.1016/j.cbi.2026.112305

Hepatocyte hnRNPK preserves mitochondrial integrity to restrain liver injury and fibrosis. (from Hepatology)
Peng Qian; Wang Sujuan; Zhang Yufeng; Luo Yangjun; Lan Beiwu — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype

This paper demonstrates mitochondrial fragmentation (via OPA1 splicing dysregulation) leading to cytosolic mtDNA release and cGAS-STING activation driving fibrotic inflammation, mechanistically paralleling the BLUE loop (VDAC1/mtDNA-cGAS-STING) in the SAMHD1 profile despite a different upstream trigger and hepatic rather than systemic context.
DOI: 10.1097/hep.0000000000001836

TANK-binding kinase 1 (TBK1): unexpected cell type-specific immune regulation beyond antiviral type I interferon signaling. (from virology/vaccinology)
Almeida Mariana S; Bezbradica Jelena S; Coban Cevayir — Current opinion in virology 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

TBK1 is the key non-canonical IKK kinase (IKKe/TBK1 partner) linking cGAS-STING/IRF3 to both IFN-I and NF-kB signaling, and this review's discussion of cell-type-specific TBK1 functions and pharmacological inhibition is directly relevant to the STING-IRF3-NFkB crosstalk axis and potential therapeutic targeting in the interferonopathy mechanism.
DOI: 10.1016/j.coviro.2026.101545

Structural and single-molecule insights into the core human mitochondrial DNA replisome. (from structural biology/biochemistry)
Plaza-G A Ismael; Miguez-Amil Samuel; Hayes Allison M; Ciesielski Grzegorz L; Fe — The Biochemical journal 2026
Score: 6/10 | Pathways: POLG-mtDNA, mito-dNTP-transport

Detailed structural insight into the Polγ/Twinkle/mtSSB replisome is directly relevant to the POLG-stalling and mtDNA replication stress steps implicated in the PURPLE pathway of this syndrome's mechanism.
DOI: 10.1042/BCJ20260373

Emerging microbiome–mitochondria crosstalk in host defense and infectious diseases: mechanistic insights into NLRP3 inflammasome activation and mtDNA-mediated immunomodulation (from Microbiology/gastroenterology (gut microbiome-mitochondria crosstalk))
Xinxing Lu; Wenbin Sun; Daowei Zhang; Bin Hou; Huiyu Tai — Frontiers in Cellular and Infection Microbiology 2026
Score: 6/10 | Pathways: NLRP3, cGAS-STING, ISG15-mitophagy, mito-ROS-NF-kB, other

Reviews mtDNA-driven cGAS-STING/NLRP3 activation and PINK1/Parkin mitophagy as general mechanisms overlapping core disease pathways, though framed via gut microbiome rather than SAMHD1-specific dysregulation.
DOI: 10.3389/fcimb.2026.1866924

cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders. (from Neurology/Neuroimmunology)
Rahim Abdul; Zubair Shaik Mahammad; Ahamed Mustak; Das Soumi; Patel Royal — 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target, clinical-phenotype

This review details cGAS-STING/mtDNA-driven neuroinflammation (Loop A) and its therapeutic targeting, relevant to the AuDHD/neurological phenotype in the SAMHD1 family though not SAMHD1-specific.
DOI: 10.1007/s11481-026-10307-9

Subacute ruminal acidosis induces colonic inflammation and barrier damage via cGAS-STING pathway in Hu sheep fed a high-grain diet. (from Veterinary gastroenterology/animal science)
Meng Meijuan; Shi Xiaoli; Tu Yuanlu; Bai Yunfeng; Chang Guangjun — 2026
Score: 6/10 | Pathways: cGAS-STING, NF-kB-IKK, treatment-target

This paper demonstrates mtDNA release triggering cGAS-STING/NF-κB pathway activation and downstream inflammation, mechanistically paralleling the BLUE loop (VDAC1/mtDNA/cGAS-STING) in the SAMHD1 syndrome model despite being an unrelated ruminant/agricultural species and disease context.
DOI: 10.1016/j.jnutbio.2026.110483

Vilazodone inhibits NLRP3 inflammasome assembly by targeting the NACHT domain and alleviates inflammatory disease. (from psychiatry/pharmacology (antidepressant drug repurposing))
Yang Xiangyu; Xiong Guifang; Yang Jie; Ma Xinyi; Qie Yuanzheng — International immunopharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Vilazodone directly inhibits NLRP3 inflammasome assembly (NACHT domain) and reduces MSU-induced inflammation, offering a potential repurposed therapeutic candidate relevant to the GOLD (uric acid/MSU-NLRP3) and general NLRP3 hyperactivation streams in this interferon-mitochondrial syndrome.
DOI: 10.1016/j.intimp.2026.117279

Novel natural inhibitor Rubimaillin targets NLRP3 R167/Y381 to ameliorate inflammatory and neurodegenerative diseases. (from Ethnopharmacology/natural product drug discovery)
Xiao Jing; Lan Zhen; Zhang Ran; Zhang Jie; Hu Zuobin — Journal of ethnopharmacology 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target

Identifies a natural NLRP3 inhibitor effective in gouty arthritis (MSU-induced, matching the GOLD pathway) and neurodegenerative models, offering a potential therapeutic candidate relevant to the NLRP3 hyperactivation axis in this syndrome.
DOI: 10.1016/j.jep.2026.122293

Lactate-Induced K370 Lactylation of STING Inhibits STING-TBK1 Signaling and Dampens Anti-Tumor Immunity. (from oncology/tumor immunometabolism)
Wu Yueyao; Wang Jingzhe; Chen Xu; Yang Yuntong; Wei Ping — Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026
Score: 6/10 | Pathways: cGAS-STING, treatment-target

Reveals a novel post-translational (lactylation) regulatory checkpoint on STING-TBK1 signaling relevant to the BLUE loop's IFN-I output, though in an oncology/tumor immunity context rather than SAMHD1 interferonopathy.
DOI: 10.1002/advs.77209

Mechanistic machine learning for prediction of prime editing outcomes. (from computational genome editing / bioengineering)
Hsu Alvin; Chen Peter J; Li Angus H; Hemez Colin F; Gao Xin D — Nature biotechnology 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

This paper presents a machine learning tool (OptiPrime) for optimizing prime editing efficiency, directly relevant to future gene correction strategies for missense mutations like SAMHD1 p.A565T, though it does not address SAMHD1 or the interferon-mitochondrial mechanism itself.
DOI: 10.1038/s41587-026-03261-7

Advances in paclitaxel-mediated remodeling of the gastric cancer immune microenvironment and sensitization to immune checkpoint inhibitors via cGAS-STING pathway activation triggered by mtDNA release: challenges and translational perspectives. (from Oncology (gastric cancer chemo-immunotherapy))
Wu Chu-Ying; Sun Zun-Long; Ye Kai — 2026
Score: 5/10 | Pathways: cGAS-STING, treatment-target, other

Describes mtDNA release activating cGAS-STING/type I interferon signaling, mechanistically overlapping with the BLUE loop, but in an oncology chemotherapy context unrelated to SAMHD1 or the family phenotype.
DOI: 10.1007/s11033-026-12570-8

Mitochondrial Dysfunction as a Driver of Meta-Inflammation in Aging: The Emerging Role of PDK4 in Bioenergetic Reprogramming and Inflammatory Amplification. (from metabolic/aging biology and endocrinology)
Chowdhury Md Riad; Jeong Gui-Hwa; Lee In-Kyu — 2026
Score: 5/10 | Pathways: NLRP3, cGAS-STING, NF-kB-IKK, mito-ROS-NF-kB, other

Reviews mitochondrial dysfunction driving NF-κB/NLRP3/cGAS-STING-mediated meta-inflammation via PDK4/pyruvate metabolism, an adjacent metabolic-inflammatory mechanism relevant to the family's mitochondrial-interferon axis but not SAMHD1-specific.
DOI: 10.3390/cells15151404

eVLP compound delivery breaks the prime editing efficiency ceiling. (from gene therapy/genome editing engineering)
Wang Margaret R; Sánchez-Rivera Francisco J — Cell genomics 2026
Score: 5/10 | Pathways: prime-editing, gene-therapy-delivery

Describes an engineered virus-like particle (eVLP) repeated-dosing strategy (PRIME-VLP) that improves prime editing efficiency, relevant as a potential future delivery platform for correcting SAMHD1 point mutations but not disease-mechanism specific.
DOI: 10.1016/j.xgen.2026.101333

🟢 Low Relevance (Score 3–4)

Potential specialty bridges — skim titles

Non-Invasive Scalp Tape-Strip RNA Sequencing Captures Disease Activity and Treatment-Response Signatures in Alopecia Areata. (from Dermatology)
Mochón-Jiménez Carmen; Gay-Mimbrera Jesús; Dávila-Flores Viviana; He Helen; Zhou — Allergy 2026
Score: 4/10 | Pathways: JAK-STAT, treatment-target

Alopecia areata tape-strip transcriptomics highlights IFN/JAK-STAT and baricitinib response signatures, mechanistically adjacent to the interferonopathy axis but not connected to SAMHD1 or the family's core mitochondrial-inflammasome pathways.
DOI: 10.1111/all.70293

Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2 (from genomics/bioinformatics methodology)
Tingting Cong; Runda Xu; Xuancheng Chen; Junsong Yuan; Zuomiao 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 SAMHD1 variants but has no direct disease mechanism or immune pathway content.
DOI: 10.1038/s41467-026-76778-9

Inflammatory kinase TBK1 suppresses homologous recombination DNA repair to sensitize tumors to chemotherapy. (from Oncology/DNA damage response)
Zhou Wei; Wang Xiangyu; Steigleder Susanne S; Xing Aowei; Yang Dan — Proceedings of the National Academy of Sciences of the United States of America 2026
Score: 4/10 | Pathways: NF-kB-IKK, other

TBK1 (IKKε/TBK1 axis) is a named kinase in the interferonopathy mechanism, but this paper focuses on its DNA-repair/chemotherapy role independent of cytokine or STING/IRF3 signaling, making it only tangentially relevant.
DOI: 10.1073/pnas.2533402123

Prime Editing Mediated Generation and Correction of the mdx5cv Mutation Restores Dystrophin Expression in Myoblasts (from Neuromuscular genetics / gene therapy)
A. Siddika; F. Husseiny; J. Rousseau; J. Tremblay — International Journal of Molecular Sciences 2026
Score: 4/10 | Pathways: prime-editing, gene-therapy-delivery

Demonstrates a generalizable prime editing correction workflow for a pathogenic point mutation restoring protein expression, methodologically relevant to future SAMHD1 A565T correction but unrelated disease (DMD) and non-immune cell type.
DOI: 10.3390/ijms27156927

In Vivo Base Editing for Neonatal Inborn Errors of Metabolism: Clinical Progress, N-of-1 Therapy, and the Ethics of Bespoke Genetic Medicine. (from Neonatology/Genetic Medicine Ethics)
Li Oscar Mingtian; Li Yijiang; Li Summer Xia Tian — Cureus 2026
Score: 4/10 | Pathways: gene-therapy-delivery, prime-editing

This paper reviews in vivo base editing for neonatal metabolic disorders using LNP delivery, relevant as a generalizable precedent for correcting a heterozygous missense variant like SAMHD1 A565T but not targeting immune/myeloid cells or the interferon-mitochondrial mechanism directly.
DOI: 10.7759/cureus.114354

From mechanical adaptation to innate immune reprogramming in osteoarthritis: a load-immunity framework (from Orthopedics/Rheumatology (mechanobiology of joint disease))
Shiguo Zuo; Lijun He; Z. Hou; Quanliang Tian; Yilong Yang — Frontiers in Immunology 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, other

This osteoarthritis review discusses cGAS-STING and NLRP3 signaling in mechanotransduction and mitochondrial danger signal propagation, mechanistically adjacent but not directly tied to SAMHD1 biology or the interferon-mitochondrial syndrome described.
DOI: 10.3389/fimmu.2026.1931112

Liver Organoids: From Disease Modelling to Regenerative Medicine. (from Hepatology/regenerative medicine)
Wang Tiepeng; Qu Xiaotian; Si Jinhong; Meng Junkang; Zhang Ting — Cell proliferation 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery

This is a general liver organoid review with only a passing mention of prime editing correction in patient-derived organoids and no SAMHD1, interferon, NLRP3, or mitochondrial dNTP pathway content relevant to the family phenotype.
DOI: 10.1111/cpr.70268

Hierarchical Core-Shell Nanoplatform with Sequential Mn<sup>2+</sup>/Co<sup>2+</sup> Release Enables Dual-Track STING Amplification and Radiosensitization for Potent Radio-Metalloimmunotherapy. (from Oncology/nanomedicine radiotherapy)
Luo Baiyi; Xiang Qingming; Xie Yingling; Wang Shuo; Xu Yu — 2026
Score: 3/10 | Pathways: cGAS-STING

Paper uses cGAS-STING pathway activation as a cancer nanomedicine strategy via metal ion delivery, unrelated to SAMHD1 mechanism or mitochondrial dNTP dysregulation despite shared pathway terminology.
DOI: 10.1016/j.actbio.2026.08.012

Estrogen Withdrawal-Induced Cognitive Impairment in Menopausal Women: Mechanisms and Prospects for Integrated Interventions. (from Neurology/Endocrinology)
Qiu Tiantian; Zhang Junying; Zhao Jiayou — International journal of molecular sciences 2026
Score: 3/10 | Pathways: NLRP3, mito-ROS-NF-kB

Discusses NLRP3 inflammasome and mitochondrial dysfunction in menopausal cognitive decline, sharing mechanistic overlap with the interferon-mitochondrial syndrome but unrelated to SAMHD1 or its specific pathways.
DOI: 10.3390/ijms27157003

The APC/C subunit APC7 exerts antiviral effects by targeting the adaptor protein MAVS (from Virology/cell biology (RIG-I-MAVS antiviral signaling))
Rui Su; Aiping Sun; Yifan Niu; Tiesuo Zhao; Hui Wang — Frontiers in Immunology 2026
Score: 3/10 | Pathways: other

This paper concerns RIG-I/MAVS antiviral signaling and IFN-I induction via a distinct APC7-MAVS ubiquitination mechanism, not overlapping with SAMHD1/cGAS-STING/NLRP3/NF-kB pathways central to the disease profile.
DOI: 10.3389/fimmu.2026.1912055

Extracellular vesicle-mediated immune crosstalk in rheumatoid arthritis synovium: mechanistic insights and translational challenges (from Rheumatology)
Feng Luo; Xuemei Yuan; Heng Zhou; Qiuyi Wang; Changming Chen — Frontiers in Immunology 2026
Score: 3/10 | Pathways: cGAS-STING, JAK-STAT, NF-kB-IKK, clinical-phenotype

This RA-focused review touches on cGAS-STING, NF-κB, and JAK-STAT signaling and mentions RA (a tracked family phenotype), but it centers on extracellular vesicle biology in synovium without any connection to SAMHD1, dNTP metabolism, or the core mitochondrial-interferon mechanism.
DOI: 10.3389/fimmu.2026.1891984

Targeting the hallmarks of ageing: Pharmacological challenges and breakthroughs in CRISPR delivery systems and future prospects. (from Gerontology/pharmacology (CRISPR delivery technology))
Rathore Sakshi; Gupta Akash; Shah Kamal; Chauhan Nagendra Singh; Gupta Sanjay Ku — Ageing research reviews 2026
Score: 3/10 | Pathways: gene-therapy-delivery, prime-editing

General CRISPR delivery/ageing review with only generic mention of prime/base editing and mitochondrial dysfunction, lacking any SAMHD1, immune, or myeloid-specific delivery focus relevant to this disease.
DOI: 10.1016/j.arr.2026.103301

Expanding the clinical spectrum of DNASE1L3-associated monogenic lupus: A case series of 4 syrian pediatric cases. (from Pediatric Rheumatology/Nephrology)
Kousa Alyamama; Alhamwi Ahmad; Alsayed Mohammad Khaled; Jabaly Sara; Khalil Bash — Medicine 2026
Score: 3/10 | Pathways: AGS-spectrum, clinical-phenotype, treatment-target

DNASE1L3 monogenic lupus is a distinct autosomal-recessive nucleic acid clearance disorder in the broader interferonopathy/autoimmune spectrum, but does not involve SAMHD1, dNTPase, cGAS-STING, or the mitochondrial-NLRP3 axis central to this profile, though baricitinib use is a tangential JAK-inhibitor overlap.
DOI: 10.1097/MD.0000000000050283

Pathway Coverage This Week

  • cGAS-STING: 13 papers
  • treatment-target: 13 papers
  • NLRP3: 7 papers
  • prime-editing: 7 papers
  • gene-therapy-delivery: 7 papers
  • NF-kB-IKK: 6 papers
  • other: 6 papers
  • mito-ROS-NF-kB: 4 papers
  • clinical-phenotype: 4 papers
  • POLG-mtDNA: 2 papers
  • urate-NLRP3: 2 papers
  • JAK-STAT: 2 papers
  • VDAC1: 1 papers
  • mito-dNTP-transport: 1 papers
  • ISG15-mitophagy: 1 papers
  • AGS-spectrum: 1 papers