ArticleeLife2021
Permeant fluorescent probes visualize the activation of SARM1 and uncover an anti-neurodegenerative drug candidate.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 71 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
- Article
- Boldine inhibits SARM1 NADase Activity and Preserves Axonal Integrity After Nerve Injury.bioRxiv : the preprint server for biology · 2026Article
- Raw defines a TIR-fold cADPR hydrolase cooperating with dSarm in development and axon degeneration.Cell communication and signaling : CCS · 2026Article
- The rise and fall of SARM1 base-exchange inhibitors.Communications chemistry · 2026Article
- SARM1 activation promotes axonal degeneration via a two-step phase transition.Nature chemical biology · 2026Article
- Programmed axon degeneration: mechanism, inhibition and therapeutic potential.Nature reviews. Neuroscience · 2026Review
- Modulating CD38 enzymatic activity during antibody-based immunotherapy in multiple myeloma: a basic science perspective.Frontiers in immunology · 2026Article
- A metabolic cell death program downstream of SARM1 couples NADProceedings of the National Academy of Sciences of the United States of America · 2025Article
- NAD + in fatty liver disease: mechanistic insights and associated targets.Cell biology and toxicology · 2025Review
- A CRISPR activation screen reveals a cilia disassembly pathway mutated in focal cortical dysplasia.Science advances · 2025Article
- SARM1 Inhibition in Three Mouse Models of Charcot-Marie-Tooth Disease.Journal of the peripheral nervous system : JPNS · 2025Article
- Genetic Deletion of Sarm1 in Mouse Models of Three Neurological Diseases.Journal of the peripheral nervous system : JPNS · 2025Article
- Therapeutic safety implications of SARM1 active site inhibitors: subinhibitory concentrations cause neurodegeneration.npj drug discovery · 2025Article
- Carnosol, a Rosemary Ingredient Discovered in a Screen for Inhibitors of SARM1-NADAntioxidants (Basel, Switzerland) · 2025Article
- SARM1 base-exchange inhibitors induce SARM1 activation and neurodegeneration at low doses.npj drug discovery · 2025Article
- Stepwise activation of SARM1 for cell death and axon degeneration revealed by a biosynthetic NMN mimic.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Gap junction intercellular communications regulates activation of SARM1 and protects against axonal degeneration.Cell death & disease · 2025Article
- Review
- Regulation of and challenges in targeting NADNature reviews. Molecular cell biology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARM1 regulates axonal degeneration through its NAD-metabolizing activity and is a drug target for neurodegenerative disorders. We designed and synthesized fluorescent conjugates of styryl derivative with pyridine to serve as substrates of SARM1, which exhibited large red shifts after conversion. With the conjugates, SARM1 activation was visualized in live cells following elevation of endogenous NMN or treatment with a cell-permeant NMN-analog. In neurons, imaging documented mouse SARM1 activation preceded vincristine-induced axonal degeneration by hours. Library screening identified a derivative of nisoldipine (NSDP) as a covalent inhibitor of SARM1 that reacted with the cysteines, especially Cys311 in its ARM domain and blocked its NMN-activation, protecting axons from degeneration. The Cryo-EM structure showed that SARM1 was locked into an inactive conformation by the inhibitor, uncovering a potential neuroprotective mechanism of dihydropyridines.
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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.