钙蛋白酶参与tau蛋白过度磷酸化和截断的机制研究进展

doi:10.3969/j.issn.1006-9771.2020.10.010

《中国康复理论与实践》 ›› 2020, Vol. 26 ›› Issue (10): 1182-1185.doi: 10.3969/j.issn.1006-9771.2020.10.010

钙蛋白酶参与tau蛋白过度磷酸化和截断的机制研究进展

郭凯文,杨翠翠,张兰()

首都医科大学宣武医院药学部,北京市神经药物工程技术研究中心,北京脑重大疾病研究院,神经变性病教育部重点实验室,北京市 100053

收稿日期:2019-08-14 修回日期:2019-12-23 出版日期:2020-10-25 发布日期:2020-10-29
通讯作者: 张兰 E-mail:lanizhg@126.com
作者简介:郭凯文(1991-),女,汉族,山东烟台市人,博士研究生,主要研究方向：神经药理学。
基金资助:
1.国家自然科学基金项目(81874351);国家自然科学基金项目(81703729);2.北京市高层次卫生技术人才计划项目(2014-2-014)

Advance in Mechanisms of Calpain Involved in Hyperphosphorylation and Truncation of Tau Protein (review)

GUO Kai-wen,YANG Cui-cui,ZHANG Lan()

Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, China

Received:2019-08-14 Revised:2019-12-23 Published:2020-10-25 Online:2020-10-29
Contact: ZHANG Lan E-mail:lanizhg@126.com
Supported by:
National Natural Science Foundation of China(81874351);National Natural Science Foundation of China(81703729);Beijing High-level Health and Technical Personal Plan(2014-2-014)

摘要/Abstract

摘要：

阿尔茨海默病(AD)是最常见的神经退行性疾病之一,临床表现为认知和记忆功能障碍。钙蛋白酶(calpain)在细胞中广泛地被激活,钙蛋白酶的紊乱会引起AD病理学中tau蛋白过度磷酸化和tau蛋白的异常剪切。钙蛋白酶通过影响糖原合成酶激酶3和蛋白磷酸酶2A的活性,从而使tau蛋白多个位点发生异常过度磷酸化,并且介导tau蛋白单体的截断,诱导神经变性。钙蛋白酶有望成为AD药物治疗的潜在靶点。

关键词: 钙蛋白酶, 阿尔茨海默病, tau蛋白, 过度磷酸化, 截断, 综述

Abstract:

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, which is characterized by cognitive and memory dysfunction. Calpain is widely activated in cells. Disturbance of calpain is currently thought to a main cause of hyperphosphorylation and abnormal cleavage of tau protein in AD pathology. Calpain affects the activities of glycogen synthase kinase 3 and protein phosphatase 2A, which causes abnormal hyperphosphorylation of multiple sites of tau protein, and mediates truncation of tau protein monomers, and induces neurodegeneration. Calpain is expected to be a potential target for drug therapy of AD.

Key words: calpain, Alzheimer's disease, tau protein, hyperphosphorylation, cleavage, review

中图分类号:

R749.16

郭凯文,杨翠翠,张兰. 钙蛋白酶参与tau蛋白过度磷酸化和截断的机制研究进展[J]. 《中国康复理论与实践》, 2020, 26(10): 1182-1185.

GUO Kai-wen,YANG Cui-cui,ZHANG Lan. Advance in Mechanisms of Calpain Involved in Hyperphosphorylation and Truncation of Tau Protein (review)[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(10): 1182-1185.

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钙蛋白酶参与tau蛋白过度磷酸化和截断的机制研究进展

Advance in Mechanisms of Calpain Involved in Hyperphosphorylation and Truncation of Tau Protein (review)

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