NIH R01 · 2024
SARM1 functional polymorphisms and their contribution to ALS risk
Motor axon loss is a cardinal symptom of amyotrophic lateral sclerosis (ALS). Axon loss can be driven by a genetically encoded program in which the axon survival factors NMNAT2 and STMN2 inhibit the activity of the axon destruction factor SARM1. Recent data suggest that this program of axon self-destruction may contribute to pathology in ALS. First, aggregation of TDP-43, a hallmark of most ALS cases, results in the selective loss of mRNA encoding functional STMN2, a key axon survival factor. Second, loss of SARM1 suppresses some neurodegenerative phenotypes in a mouse ALS model that expresses pathogenic human TDP-43. Here we investigate the contribution of this axon degeneration pathway to…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.