CADPR is a gene dosage-sensitive biomarker of SARM1 activity in healthy, compromised, and degenerating axons.

ABSTRACT: SARM1 is the central executioner of pathological axon degeneration, promoting axonal demise in response to axotomy, traumatic brain injury, and neurotoxic chemotherapeutics that induce peripheral neuropathy. SARM1 is an injury-activated NAD⁺ cleavage enzyme, and this NADase activity is required for the pro-degenerative function of SARM1. At present, SARM1 function is assayed by either analysis of axonal loss, which is far downstream of SARM1 enzymatic activity, or via NAD⁺ levels, which are regulated by many competing pathways. Here we explored the utility of measuring cADPR, a product of SARM1-dependent cleavage of NAD⁺, as an in cell and in vivo biomarker of SARM1 enzymatic activity. We find that SARM1 is a major producer of cADPR in cultured dorsal root

SUBMITTER: Sasaki Y 

PROVIDER: S-EPMC7302925 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature