Neurofibrillary tangles (NFTs) are one of the neuro-pathological hallmarks ofAlzheimer's disease (AD) and abnormally hyperphosphorylated tau is the major protein of NFTs It wasreported that cyclin-dependent kinase...Neurofibrillary tangles (NFTs) are one of the neuro-pathological hallmarks ofAlzheimer's disease (AD) and abnormally hyperphosphorylated tau is the major protein of NFTs It wasreported that cyclin-dependent kinase5 (Cdk-5) could phosphorylate tau atmost AD-related epitopesin vivo. In this study, we investigated the effect of cdk-5 overexpression on tauhyperphosphbrylation in neuroblastoma N2a cells. We demonstrated that Overexpression of cdk-5 whichresulted in a 3.5-fold Cdk-5 activation in thetransfected cells induced a dramatic increase inphosphorylation of tau at severalphosphorylatiosites. Overexpression of cdk-5 led to a reducedstaining with antibody Tau-1 and an enhanced staining with antibody PHF-1, suggestinghy-perphosphorylation of tau at Serl99/202 and Ser396/404 sites. It implies that in vitroOverexpression of cdk-5 leads to Cdk-5 overactivation and tau hyperphosphorylation may be theunderline mechanism.展开更多
基金Supported by the National Natural Science Foundation of China (39925012 30100057+1 种基金30170221) the Science and Technology Founda tion Committee Foundurion of China(G1999054007) and National Youth Sci ence Foundation of China(39925012)
文摘Neurofibrillary tangles (NFTs) are one of the neuro-pathological hallmarks ofAlzheimer's disease (AD) and abnormally hyperphosphorylated tau is the major protein of NFTs It wasreported that cyclin-dependent kinase5 (Cdk-5) could phosphorylate tau atmost AD-related epitopesin vivo. In this study, we investigated the effect of cdk-5 overexpression on tauhyperphosphbrylation in neuroblastoma N2a cells. We demonstrated that Overexpression of cdk-5 whichresulted in a 3.5-fold Cdk-5 activation in thetransfected cells induced a dramatic increase inphosphorylation of tau at severalphosphorylatiosites. Overexpression of cdk-5 led to a reducedstaining with antibody Tau-1 and an enhanced staining with antibody PHF-1, suggestinghy-perphosphorylation of tau at Serl99/202 and Ser396/404 sites. It implies that in vitroOverexpression of cdk-5 leads to Cdk-5 overactivation and tau hyperphosphorylation may be theunderline mechanism.
