ArticleThe Journal of cell biology2020
SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Nerve pathology and neuropathic pain after whiplash injury: a systematic review and meta-analysis.Pain · 2022Pooled it
- Oxidative signaling thresholds shape vulnerability in the central and peripheral nervous systems.PLoS biology · 2026Article
- Direct activation of SARM1 by dsDNA is not supported by biochemical and cellular evidence.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Review
- Loss of SARM1 Improves Phenotypes in a Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.Neurology. Genetics · 2026Article
- hUC-MSCs via β-NGF Alleviate Cognitive Impairment After Tibial Fracture Surgery by Regulating the STMN2/NMNAT2-SARM1-NF-κB Signaling Pathway.CNS neuroscience & therapeutics · 2026Article
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Caspase-3 cleaves and activates the NADase SARM1 to promote apoptosis, linking two cell death mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hyperglycemia promotes SIRT3-mediated deacetylation of SARM1 to exacerbate diabetic peripheral neuropathy in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Regulatory complexity and therapeutic targeting of the necroptosis network.Frontiers in immunology · 2026Review
- Emerging Roles of Regulated Cell Death-mediated Inflammation in Pathophysiology of Ocular Diseases.Journal of ophthalmic & vision research · 2026Review
- IL1A enhances TNF-induced retinal ganglion cell death.Frontiers in aging neuroscience · 2026Article
- Intravitreal injection of SARM1 siRNA in TNF-induced optic nerve degeneration.International ophthalmology · 2025Article
- Modeling neurodegeneration in the retina and strategies for developing pan-neurodegenerative therapies.Molecular neurodegeneration · 2025Review
- SARM1: The Checkpoint of Axonal Degeneration in the Nervous System Disorders.Molecular neurobiology · 2025Review
- Carnosol, a Rosemary Ingredient Discovered in a Screen for Inhibitors of SARM1-NADAntioxidants (Basel, Switzerland) · 2025Article
- Evolutionarily ancient functions of enzymatic TIR proteins in innate immunity.Trends in immunology · 2025Review
- Managing surface energy dynamics for enhanced axonal growth: An overview of present and future challenges.Biophysics reviews · 2025Review
- Genetic Ablation of Sarm1 Mitigates Disease Acceleration after Traumatic Brain Injury in the SOD1Annals of neurology · 2025Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Neuroinflammation and necroptosis are major contributors to neurodegenerative disease, and axon dysfunction and degeneration is often an initiating event. SARM1 is the central executioner of pathological axon degeneration. Here, we demonstrate functional and mechanistic links among these three pro-degenerative processes. In a neuroinflammatory model of glaucoma, TNF-α induces SARM1-dependent axon degeneration, oligodendrocyte loss, and subsequent retinal ganglion cell death. TNF-α also triggers SARM1-dependent axon degeneration in sensory neurons via a noncanonical necroptotic signaling mechanism. MLKL is the final executioner of canonical necroptosis; however, in axonal necroptosis, MLKL does not directly trigger degeneration. Instead, MLKL induces loss of the axon survival factors NMNAT2 and STMN2 to activate SARM1 NADase activity, which leads to calcium influx and axon degeneration. Hence, these findings define a specialized form of axonal necroptosis. The demonstration that neuroinflammatory signals and necroptosis can act locally in the axon to stimulate SARM1-dependent axon degeneration identifies a therapeutically targetable mechanism by which neuroinflammation can stimulate axon loss in neurodegenerative disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.