SARM1 is required in human derived sensory neurons for injury-induced and neurotoxic axon degeneration.

ABSTRACT: Axonal degeneration contributes to the pathogenesis of many neurodegenerative disorders, motivating efforts to dissect the mechanism of pathological axon loss in order to develop therapies for axonal preservation. SARM1 is a particularly attractive therapeutic target, as it is an inducible NAD⁺ cleaving enzyme that is required for axon loss in multiple mouse models of traumatic and degenerative neurological disease. However, it is essential to establish whether SARM1 triggers axon degeneration in human neurons before proceeding with the development of SARM1-directed therapeutics. Here we combine genome engineering with the production of human stem cell-derived neurons to test the role of human SARM1 in traumatic and neurotoxic axon degeneration. We have generated two independent

SUBMITTER: Chen YH 

PROVIDER: S-EPMC8171232 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature