Cytosolic phospholipase A2 links tau pathology to insulin signaling impairment in Alzheimer's disease.

ABSTRACT: Although impaired insulin signaling in the brain has been recognized as a key factor in the development and progression of Alzheimer's disease (AD), the underlying mechanisms remain incompletely understood. Given that overactivation of cytosolic phospholipase A2 (cPLA2) has been implicated in AD, we tested the hypothesis that oligomeric tau (oTau) activates cPLA2, which in turn negatively affects Caveolin-1 (Cav-1) and insulin signaling. In the cerebral cortex and hippocampus of 12-months-old 3xTg-AD mice, we observed an upregulation of phosphorylated cPLA2 (p-cPLA2), accompanied by downregulation of Cav-1 and impaired insulin signaling. Specifically, we found significant decreases in insulin receptor-α (IR-α) and insulin receptor-β (IR-β) expression, along with increased levels of phospho

SUBMITTER: Hossen F 

PROVIDER: S-EPMC12634615 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature