ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Sarm1-mediated axon degeneration requires both SAM and TIR interactions.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.
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Who cites it
237 citing papers in PubMed, 394 citations in OpenAlex.
- 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
- Nicotinamide Mononucleotide Adenylyltransferase 1 and NADMetabolites · 2026Review
- Review
- Peripheral Neuropathy in Metabolic Stress.International journal of molecular sciences · 2026Review
- Enhancing peripheral nerve regeneration in aging: the role of Schwann cells, c-Jun, and emerging therapeutic strategies.GeroScience · 2026Review
- The rise and fall of SARM1 base-exchange inhibitors.Communications chemistry · 2026Article
- Macrophage metabolic exhaustion and PANoptotic cell death drive chronic tissue inflammation in rheumatoid arthritis.Immunity · 2026Article
- SARM1 activation promotes axonal degeneration via a two-step phase transition.Nature chemical biology · 2026Article
- AxoMetric platform facilitates rapid and unbiased automated quantification of axon regeneration in tissue sections.Cell reports methods · 2026Article
- 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
- Programmed axon degeneration: mechanism, inhibition and therapeutic potential.Nature reviews. Neuroscience · 2026Review
- New mechanistic insight into SARM1 activation: TRIM32-mediated ubiquitination is a key lever that actuates SARM1's catalytic action, leading to axon degeneration and cell death.Frontiers in neural circuits · 2026Article
- Vincristine-induced brain toxicity is reduced with prevention of peripheral axon degeneration in Sarm1 knockout mice.Acta neuropathologica communications · 2025Article
- A metabolic cell death program downstream of SARM1 couples NADProceedings of the National Academy of Sciences of the United States of America · 2025Article
- APLP1 Interacts with SARM1 and Regulates Axonal Maintenance and Post-Injury Degeneration.Molecular neurobiology · 2025Article
- Cancer cell death induced by the NAD antimetabolite Vacor discloses the antitumor potential of SARM1.FEBS letters · 2025Article
- A CRISPR activation screen reveals a cilia disassembly pathway mutated in focal cortical dysplasia.Science advances · 2025Article
- Deletion of murineScience translational medicine · 2025Article
- SARM1 Inhibition in Three Mouse Models of Charcot-Marie-Tooth Disease.Journal of the peripheral nervous system : JPNS · 2025Article
177 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Axon degeneration is an evolutionarily conserved pathway that eliminates damaged or unneeded axons. Manipulation of this poorly understood pathway may allow treatment of a wide range of neurological disorders. In an RNAi-based screen performed in cultured mouse DRG neurons, we observed strong suppression of injury-induced axon degeneration upon knockdown of Sarm1 [SARM (sterile α-motif-containing and armadillo-motif containing protein)]. We find that a SARM-dependent degeneration program is engaged by disparate neuronal insults: SARM ablation blocks axon degeneration induced by axotomy or vincristine treatment, while SARM acts in parallel with a soma-derived caspase-dependent pathway following trophic withdrawal. SARM is a multidomain protein that associates with neuronal mitochondria. Deletion of the N-terminal mitochondrial localization sequence disrupts SARM mitochondrial localization in neurons but does not alter its ability to promote axon degeneration. In contrast, mutation of either the SAM (sterile α motif) or TIR (Toll-interleukin-1 receptor) domains abolishes the ability of SARM to promote axonal degeneration, while a SARM mutant containing only these domains elicits axon degeneration and nonapoptotic neuronal death even in the absence of injury. Protein-protein interaction studies demonstrate that the SAM domains are necessary and sufficient to mediate SARM-SARM binding. SARM mutants lacking a TIR domain bind full-length SARM and exhibit strong dominant-negative activity. These results indicate that SARM plays an integral role in the dismantling of injured axons and support a model in which SAM-mediated multimerization is necessary for TIR-dependent engagement of a downstream destruction pathway. These findings suggest that inhibitors of SAM and TIR interactions represent therapeutic candidates for blocking pathological axon loss and neuronal cell death.
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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.