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

Autor: Feng Youmei, Wang Jian-zhi, Chen Juan, Li Hong-lian
Rok vydání: 2005
Předmět:
Zdroj: Wuhan University Journal of Natural Sciences. 10:472-476
ISSN: 1993-4998
1007-1202
DOI: 10.1007/bf02830689
Popis: 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.
Databáze: OpenAIRE