The SARM1 axon degeneration pathway: control of the NAD+ metabolome regulates axon survival in health and disease

Matthew D. Figley, Aaron DiAntonio

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

Axons are essential for nervous system function and axonal pathology is a common hallmark of many neurodegenerative diseases. Over a century and a half after the original description of Wallerian axon degeneration, advances over the past five years have heralded the emergence of a comprehensive, mechanistic model of an endogenous axon degenerative process that can be activated by both injury and disease. Axonal integrity is maintained by the opposing actions of the survival factors NMNAT2 and STMN2 and pro-degenerative molecules DLK and SARM1. The balance between axon survival and self-destruction is intimately tied to axonal NAD+ metabolism. These mechanistic insights may enable axon-protective therapies for a variety of human neurodegenerative diseases including peripheral neuropathy, traumatic brain injury and potentially ALS and Parkinson's.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalCurrent Opinion in Neurobiology
Volume63
DOIs
StatePublished - Aug 2020

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