细胞周期蛋白依赖性激酶5（Cdk5），阿尔茨海默病的一个治疗靶点？

Cdk5, a therapeutic target for Alzheimer's disease?

作者信息

Tsai Li-Huei, Lee Ming-Sum, Cruz Jonathan

机构信息

Department of Pathology, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA 02115, USA.

出版信息

Biochim Biophys Acta. 2004 Mar 11;1697(1-2):137-42. doi: 10.1016/j.bbapap.2003.11.019.

DOI:10.1016/j.bbapap.2003.11.019

PMID:15023356

Abstract

Alzheimer's disease (AD) represents the leading cause for senile dementia affecting more than 4 million people worldwide. AD patients display a triad of pathological features including brain atrophy caused by neuronal loss, beta-amyloid plaque and neurofibrillary tangles. We previously show that Cyclin-dependent kinase 5 (Cdk5) is deregulated in AD brains and may contribute to the pathogenesis of AD. In AD brains, a calpain cleavage product of its physiological regulator p35, p25 is elevated. p25 causes prolonged activation of Cdk5 and alteration of its substrate specificity. The implications of p25/Cdk5 in neurotoxicity, beta-amyloid plaque and neurofibrillary tangle pathology will be discussed.

摘要

阿尔茨海默病（AD）是导致老年痴呆的主要原因，全球有超过400万人受其影响。AD患者表现出三联病理特征，包括因神经元丢失导致的脑萎缩、β-淀粉样蛋白斑块和神经原纤维缠结。我们之前表明，细胞周期蛋白依赖性激酶5（Cdk5）在AD大脑中失调，可能促成AD的发病机制。在AD大脑中，其生理调节因子p35的钙蛋白酶裂解产物p25水平升高。p25导致Cdk5的持续激活及其底物特异性改变。将讨论p25/Cdk5在神经毒性、β-淀粉样蛋白斑块和神经原纤维缠结病理学中的影响。