SARM1

Sterile alpha and TIR motif containing 1 (SARM1), commonly called SARM, is a key regulator of axonal degeneration. Its TIR domain has NADase activity; axonal injury activates SARM1 to rapidly hydrolyze NAD+, depleting cellular energy reserves and triggering axon death—this mechanism underlies Wallerian degeneration and pathogenic axon loss in neurological disorders.
SARM1 dysregulation links to amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and peripheral neuropathy. Small-molecule inhibitors targeting its NADase activity have shown preclinical efficacy, with several candidates advancing toward early clinical trials for treating these axonopathy-related diseases.