ArticleMolecular neurodegeneration2022
Constitutively active SARM1 variants that induce neuropathy are enriched in ALS patients.
Article in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 117 citations in OpenAlex.
- Nicotinamide Mononucleotide Adenylyltransferase 1 and NADMetabolites · 2026Review
- SARM1 activation promotes axonal degeneration via a two-step phase transition.Nature chemical biology · 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
- An in silico protocol for predicting genetic biomarkers in rare diseases: a case study in sporadic amyotrophic lateral sclerosis.Frontiers in genetics · 2026Article
- Programmed axon degeneration: mechanism, inhibition and therapeutic potential.Nature reviews. Neuroscience · 2026Review
- Dysregulated lactate metabolism synergizes with ALS genetic risk factors to accelerate motor decline.PloS one · 2026Article
- Dysregulated lactate metabolism synergizes with ALS genetic risk factors to accelerate motor decline.bioRxiv : the preprint server for biology · 2025Article
- A redox-dependent switch governing sensory axon degeneration and regeneration.Scientific reports · 2025Article
- A CRISPR activation screen reveals a cilia disassembly pathway mutated in focal cortical dysplasia.Science advances · 2025Article
- Pyruvate kinase deficiency links metabolic perturbations to neurodegeneration and axonal protection.Molecular metabolism · 2025Article
- SARM1: The Checkpoint of Axonal Degeneration in the Nervous System Disorders.Molecular neurobiology · 2025Review
- Suppressing phagocyte activation by overexpressing the phosphatidylserine lipase ABHD12 preserves sarmopathic nerves.iScience · 2025Article
- Genetic Ablation of Sarm1 Mitigates Disease Acceleration after Traumatic Brain Injury in the SOD1Annals of neurology · 2025Article
- Toll-1-dependent immune evasion induced by fungal infection leads to cell loss in the Drosophila brain.PLoS biology · 2025Article
- Gap junction intercellular communications regulates activation of SARM1 and protects against axonal degeneration.Cell death & disease · 2025Article
- Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.Current protein & peptide science · 2025Review
- Review
- SARM1: a key multifaceted component in immunoregulation, inflammation and neurodegeneration.Frontiers in immunology · 2025Review
- Review
- Exploring clinical markers of Axon degeneration processes in Chemotherapy-induced peripheral neuropathy among young adults receiving vincristine or paclitaxel.BMC neurology · 2024Observational
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIn response to injury, neurons activate a program of organized axon self-destruction initiated by the NAD
methodsTo investigate whether naturally occurring human variants might disrupt SARM1 autoinhibition and potentially contribute to risk for neurodegenerative disease, we assayed the enzymatic activity of all 42 rare SARM1 alleles identified among 8507 amyotrophic lateral sclerosis (ALS) patients and 9671 controls. We then intrathecally injected mice with virus expressing SARM1 constructs to test the capacity of an ALS-associated constitutively active SARM1 variant to promote neurodegeneration in vivo.
resultsTwelve out of 42 SARM1 missense variants or small in-frame deletions assayed exhibit constitutive NADase activity, including more than half of those that are unique to the ALS patients or that occur in multiple patients. There is a > 5-fold enrichment of constitutively active variants among patients compared to controls. Expression of constitutively active ALS-associated SARM1 alleles in cultured dorsal root ganglion (DRG) neurons is pro-degenerative and cytotoxic. Intrathecal injection of an AAV expressing the common SARM1 reference allele is innocuous to mice, but a construct harboring SARM1
conclusionsThese results implicate rare hypermorphic SARM1 alleles as candidate genetic risk factors for ALS and other neurodegenerative conditions.
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