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

Neurofibrillary tangles (NFTs) are one of the neuropathological 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 whieh rcsul-ted 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 Ser199/202 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.

The effect ofcdk-5 overexpression and overactivation on tau hyperphosphorylation in cultured N2a cells

Neurofibrillary tangles (NFTs) are one of the neuropathological 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 ofcdk-5 overexpression on tau hyperphosphorylation in neuroblastoma N2a cells. We demonstrated that overexpression ofcdk-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 ofcdk-5 led to a reduced staining with antibody Tau-1 and an enhanced staining with antibody PHF-1, suggesting hyperphosphorylation of tau at Ser 199/202 and Ser396/404 sites. It implies that in vitro overexpression ofcdk-5 leads to Cdk-5 overactivation and tau hyperphosphorylation may be the underline mechanism. Foundation item: Supported by the National Natural Science Foundation of China (39925012, 3010057, 30170221), the Science and Technology Foundation Committee Foundurion of China (G1999054007) and National Youth Science Foundation of China (39925012) Biography: CHEN Juan (1969-) female, Ph.D, research direction: neurology and Alzheimer's disease.