Pharmacological SARM1 inhibition protects axon structure and function in paclitaxel-induced peripheral neuropathy.

ABSTRACT: Axonal degeneration is an early and ongoing event that causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems. Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of morbidity and the main cause of dose reductions and discontinuations in cancer treatment. Preclinical evidence indicates that activation of the Wallerian-like degeneration pathway driven by sterile alpha and TIR motif containing 1 (SARM1) is responsible for axonopathy in CIPN. SARM1 is the central driver of an evolutionarily conserved programme of axonal degeneration downstream of chemical, inflammatory, mechanical or metabolic insults to the axon. SARM1 contains an intrinsic NADase enzymatic activity essential for its pro-degenerative function

SUBMITTER: Bosanac T 

PROVIDER: S-EPMC8634121 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature