Cdk5 as a drug target for the treatment of Alzheimer's disease

被引：62

作者：

Lau, LF ^{[1
]}

Seymour, PA ^{[1
]}

Sanner, MA ^{[1
]}

Schachter, JB ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, CNS Discovery, Groton, CT 06340 USA

来源：

JOURNAL OF MOLECULAR NEUROSCIENCE | 2002年 / 19卷 / 03期

关键词：

tau phosphorylation; cdk5; p25; p35; calpain; Alzheimer's disease; neurofibrillary tangles; kinase; paired helical filament; neurodegeneration; microtubules; cytoskeleton; pretangle;

D O I：

10.1385/JMN:19:3:267

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cyclin-dependent kinase-5 (cdk5) is suggested to play a role in tau phosphorylation. and contribute to the pathogenesis of Alzheimer's disease (AD). One of its activators, p25, is dramatically increased in AD brains where p25 and cdk5 are colocalized with neurofibrillary tangles. Several animal models have shown a correlation of p25 / cdk5 activities with tau phosphorylation. Overexpression. of p25 / cdk5 in nueronal cultures not only leads to tau phosphorylation but also cytoskeletal abnormalities and neurodegeneration. Therefore, cdk5 kinase inhibitors are potential therapeutic agents for the treatment of AD. Availability of potent, selective, brain permeable cdk5 inhibitors and relevant animal models in which their efficacy can be treated will be critical in the development of these inhibitors.

引用

页码：267 / 273

页数：7

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