Constitutively active SARM1 variants found in ALS patients induce neuropathy

摘要

2021 MAY 05 (NewsRx) - By a News Reporter-Staff News Editor at Disease Prevention Daily - According to news reporting based on a preprint abstract, our journalists obtained the following quote sourced from biorxiv.org: "In response to injury, neurons activate a program of organized axon self-destruction initiated by the NAD+ hydrolase SARM1. "In healthy neurons SARM1 is autoinhibited, but single amino acid changes can abolish autoinhibition leading to constitutively-active SARM1 enzymes that promote degeneration when expressed in cultured neurons. "To investigate whether naturally-occurring human variants might similarly disrupt SARM1 autoinhibition and potentially contribute to risk for neurodegenerative disease, we assayed the enzymatic activity of 29 rare SARM1 alleles identified among 8,507 amyotrophic lateral sclerosis (ALS) patients.