摘要
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.
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.
基金
Supported by the National Natural Science Foundation of China (39925012
30100057
30170221)
the Science and Technology Founda tion Committee Foundurion of China(G1999054007) and National Youth Sci ence Foundation of China(39925012)
