RNF168 dephosphorylation ameliorates cognitive decline in Aβ-based mouse models of Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder among the elderly, with limited effective treatments available in clinical practice. Impaired glucose metabolism has long been observed in the brains of AD patients, yet the mechanisms linking metabolic signals to AD pathogenesis remain elusive. Our previous study demonstrated that growth signals regulate genomic stability through RNF168 phosphorylation. Here, we report that phosphorylation of RNF168 at Ser60 is significantly elevated in the hippocampi of Aβ-based mouse models of AD. Genetic dephosphorylation of RNF168 S60 enhances DNA damage response, reduces double-strand breaks (DSBs), and ameliorates learning and memory deficits in Aβ-based mouse models of AD. Mechanistically, RNF168 S60 phosphorylation impairs l

SUBMITTER: Ji MJ 

PROVIDER: S-EPMC12462251 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature