Caspase-3 cleaves and activates the NADase SARM1 to promote apoptosis, linking two cell death mechanisms.

ABSTRACT: Two major mechanisms of axon degeneration have been identified. The first, a caspase-dependent apoptotic pathway, is a major mediator of developmental axon degeneration triggered by loss of trophic support. The second, a caspase-independent pathway mediated by the sterile alpha and HEAT/Armadillo motif containing 1 (SARM1) NADase, was found in studies of injury-induced Wallerian degeneration; it is also implicated in degeneration associated with traumatic brain injury, as well as some neurodegenerative diseases and neuropathies. Recent studies suggest that SARM1 functions as a metabolic sensor for the cellular nicotinamide mononucleotide/NAD+ ratio through its autoinhibitory armadillo repeats (ARM) domain. Here, we show a tight link between apoptotic and SARM1-dependent degeneration by dem

SUBMITTER: Shi J 

PROVIDER: S-EPMC12846840 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature