Sterile alpha and TIR motif-containing protein 1 (SARM1)

Sterile alpha and TIR motif-containing protein 1 (SARM1) is an essential enzyme in the nervous system, primarily responsible for programmed axon degeneration via NAD+ hydrolysis, making it a central regulator of axon survival and death. It belongs to the TIR-domain family of NAD+ hydrolases and has additional adaptor signal transduction roles in Toll-like receptor pathways affecting innate immunity. SARM1 activity is tightly regulated by cellular NAD+ and NMN levels, and dysregulation has been implicated in pathological neurodegeneration, offering potential pharmacological avenues for treating neurodegenerative diseases and injuries. Activators such as Vacor and 3-acetylpyridine promote SARM1 activity and axon loss, while inhibitors counteract its pathological effects. SARM1 also has roles in neuronal development and immune signaling, which broaden its therapeutic relevance.

Other names

Sterile alpha and TIR motif containing 1SARM1Sterile alpha and HEAT/Armadillo motif containing 1TIR-domain NAD+ hydrolase

Inhibition of NADase activity (neuroprotection); Activation of NADase activity (axon degeneration induction, neurotoxic)