Activating Mutations of Sarm1 Enriched in ALS

Sarm1 mutations are not common in ALS patients, but a careful examination of the ones that do occur by Dr. Joseph Bloom and colleagues has shown that they tend to cause Sarm1 to be constitutively active and occur more frequently in ALS patients than in the general population. This research, published in Molecular Neurodegeneration, suggests […]

Protein structure studies demonstrate how SARM1 senses cellular energy status to trigger axon degeneration

Two recent articles published by Needleman Center researchers dissect the structure of SARM1, an enzyme responsible for initiating programmed axon degeneration, and shed light on how the balance of key cellular metabolites regulate its activity. SARM1 forms an octamer in which each monomer contains an N-terminal autoinhibitory domain, domains that mediate multimerization, and a C-terminal […]

Mouse model provides hope to treat a rare form of congenital blindness

Leber congenital amaurosis (LCA) type nine is an autosomal recessive retinopathy leading to early childhood blindness caused by mutations of the NAD+ synthesis enzyme NMNAT1. In work lead by Dr. Yo Sasaki and published in the journal Elife, Needleman Center researchers demonstrated that loss of NMNAT1 leads to activation of the SARM1-mediated axon degeneration pathway in photoreceptors. Loss […]