Tri-snRNP activity modulates tauopathy phenotypes.

ABSTRACT: Alzheimer's disease (AD) and other tauopathies are neurodegenerative disorders with devastating consequences for cognition and memory. Pathogenic accumulation of tau can be modeled in Caenorhabditis elegans, which recapitulate human neurodegeneration including aging-dependent accumulation of phosphorylated tau, tau aggregation, neuronal dysfunction, and neuron degeneration. Using forward genetic screens to identify genes modulating tau pathology, we identified a single point mutation in dib-1 that ameliorates tau-driven behavioral defects, prevents neurodegeneration, and decreases tau protein levels. The dib-1 gene encodes a small, highly conserved protein, known as TXNL4A in humans, and participates in mRNA splicing via the U4/U6.U5 tri-snRNP. Notably, heterozygous lo

SUBMITTER: LeBlanc KR 

PROVIDER: S-EPMC12469191 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature