Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration.

ABSTRACT: Aging is the biggest risk factor for the development of Alzheimer's disease (AD). Here, we performed a whole-genome CRISPR screen to identify regulators of neuronal age and show that the neddylation pathway regulates both cellular age and AD neurodegeneration in a human stem cell model. Specifically, we demonstrate that blocking neddylation increased cellular hallmarks of aging and led to an increase in Tau aggregation and phosphorylation in neurons carrying the APP^swe/swe mutation. Aged APP^swe/swe but not isogenic control neurons also showed a progressive decrease in viability. Selective neuronal loss upon neddylation inhibition was similarly observed in other isogenic AD and in Parkinson's disease (PD) models, including PSEN^M146V/M146V cortical and LRRK2<

SUBMITTER: Saurat N 

PROVIDER: S-EPMC11405001 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature