SARM1 participates in axonal degeneration and mitochondrial dysfunction in prion disease.

ABSTRACT: Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss, axonal degeneration, and mitochondrial dysfunction. Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1. We found that depletion or dysfunctional mutation of SARM1 protected against NAD⁺ loss, axonal degeneration, and mitochondrial functional disorder induced by the neurotoxic peptide PrP^106-126. NAD⁺ supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect. NAD⁺ supplementation in PrP^106-126-incubated N2a cells, SARM1 depletion, and SARM1 dysfunctional mutation each blocked neuronal a

SUBMITTER: Lai MY 

PROVIDER: S-EPMC9083142 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature