SARM1 signaling mechanisms in the injured nervous system

Shilpa Sambashivan, Marc R. Freeman

Research output: Contribution to journalReview articlepeer-review

Abstract

Axon degeneration is a prominent feature of the injured nervous system, occurs across neurological diseases, and drives functional loss in neural circuits. We have seen a paradigm shift in the last decade with the realization that injured axons are capable of actively driving their own destruction through the sterile-alpha and TIR motif containing 1 (SARM1) protein. Early studies of Wallerian degeneration highlighted a central role for NAD+ metabolites in axon survival, and this association has grown even stronger in recent years with a deeper understanding of SARM1 biology. Here, we review our current knowledge of SARM1 function in vivo and our evolving understanding of its complex architecture and regulation by injury-dependent changes in the local metabolic environment. The field is converging on a model whereby SARM1 acts as a sensor for metabolic changes that occur after injury and then drives catastrophic NAD+ loss to promote degeneration. However, a number of observations suggest that SARM1 biology is more complicated, and there remains much to learn about how SARM1 governs nervous system responses to injury or disease.

Original languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalCurrent Opinion in Neurobiology
Volume69
DOIs
StatePublished - Aug 2021

ASJC Scopus subject areas

  • Neuroscience(all)

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