A survey of Cdk5 activator p35 and p25 levels in Alzheimer's disease brains

FEBS Letters

Shen, Yong²  Tseng, Huang-Chun¹  Tsai, Li-Huei¹  Zhou, Ying¹ 

[1] Howard Hughes Medical Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA;Haledman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, AZ 85351, USA

关键词: Cyclin-dependent kinase 5;    Cyclin-dependent kinase 5 activator;    Proteolysis;    Alzheimer's disease;   

DOI  :  10.1016/S0014-5793(02)02934-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

P25, a calpain cleavage product of the cyclin-dependent kinase 5 (Cdk5) activator p35, causes prolonged activation of Cdk5. Although p25 has been shown to accumulate in brains of patients with Alzheimer's disease (AD), it is not known whether p25 accumulation in AD is brain region-specific. We analyzed the amounts of p25 and p35 in human autopsy samples from multiple brain regions including frontal cortex, inferior parietal cortex and hippocampus using immunoblotting assays. Our results show that the p25–p35 indices are higher in AD than in the control groups in all three brain regions. The most significant difference in p25–p35 indices between AD and control groups is in the frontal cortex. No significant difference in calpain activity between AD and control groups is observed, indicating that postmortem calpain activation cannot account for the elevation of p25/p35 ratios in AD brains. Our results support the notion that p25 accumulation deregulates Cdk5 activity in AD brains, and the deregulated Cdk5 activity may contribute to the pathogenesis of AD.

【 授权许可】

Unknown