The Effect of cdk - 5 Overexpression and Overactivation on Tau Hyperphosphorylation in Cultured N2a Cells

摘要

Neurofibrillary tangles (NFTs) are one of the neuro-pathological hallmarks of Alzheimer's disease (AD) and abnormally hyperphosphorylated tau is the major protein of NFTs. It was reported that cyclin-dependent kinase5 (Cdk-5) could phosphorylate tau at most AD-related epitopes in vivo. In this study, we investigated the effect of cdk-5 Overexpression on tau hyperphosphorylation in neuroblastoma N2a cells. We demonstrated that Overexpression of cdk_5 which resulted in a 3. 5-fold Cdk-5 activation in the transfected cells induced a dramatic increase in phosphorylation of tau at several phosphorylation sites, Overexpression of cdk-5 led to a reduced staining with antibody Tau-1 and an enhanced staining with antibody PHF-1, suggesting hyperphosphorylation of tau at Serl99/202 and Ser396/404 sites. It implies that in vitro Overexpression of cdk-5 leads to Cdk-5 overactivation and tau hyperphosphorylation may be the underline mechanism.