SARM1 is responsible for calpain-dependent dendrite degeneration in mouse hippocampal neurons

Sterile alpha and TIR motif containing 1 (SARM1) is a critical regulator of axon degeneration that acts through hydrolysis of NAD+ following injury. Recent work has defined the mechanisms underlying SARM1’s catalytic activity and advanced our understanding of SARM1 function in axons, yet the role of SARM1 signaling in other compartments of neurons is still not well understood. Here we show in cultured hippocampal neurons that endogenous SARM1 is present in axons, dendrites and cell bodies and that direct activation of SARM1 by the neurotoxin Vacor causes not just axon degeneration, but degeneration of all neuronal compartments. In contrast to the axon degeneration pathway defined in dorsal root ganglia (DRGs), SARM1-dependent hippocampal axon degeneration in vitro is not sensitive to calpain inhibition whereas dendrite degeneration downstream of SARM1 is calpain-dependent in this cell type. This data indicates SARM1 plays a critical role in neurodegeneration outside of axons and elucidates divergent pathways leading to degeneration in hippocampal axons and dendrites.

• Publication year

  2023

• Venue

  bioRxiv

• Publication date

  2023-07-19

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.jbc.2024.105630PMID 38199568PMCID 10862016
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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