Rejuvenating aged microglia by p16^ink4a-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer's disease.

ABSTRACT: Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer's disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16^ink4a), a cell cycle factor related to aging. We found that p16^ink4a expression

SUBMITTER: Shin HJ 

PROVIDER: S-EPMC10943801 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature