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CREB转录共激活因子1在神经退行性相关疾病中的研究进展

薛占成, 王闯, 王钦文, 张俊芳

宁波大学医学院，宁波 315211；浙江省病理生理技术重点实验室，宁波 315211

摘要

cAMP反应元件结合蛋白(cAMP-responsive element binding protein, CREB)作为转录因子，促进启动子中具有cAMP反应元件(cAMP response element, CRE)的基因转录。近年的研究显示，CREB转录共激活因子(CREB-regulated transcription coactivator, CRTC；又名transducer of regulated CREB, TORC)家族可以显著增强CREB靶基因的转录。CRTC家族有3个成员(CRTC1~3)，其中CRTC1在脑组织中高表达。一些研究表明CRTC1在神经元树突生长发育、长时程突触可塑性、记忆巩固和再巩固等过程中发挥重要作用；且在神经退行性相关疾病等发病过程中出现表达或活性异常。本文主要针对CRTC1表达或活性异常在神经退行性相关疾病发病过程中的作用及分子机制做一综述。

关键词： CREB转录共激活因子1; cAMP反应元件结合蛋白; CRE靶基因转录; 神经退行性疾病; 阿尔茨海默病; 亨廷顿病

分类号：R329

CREB-regulated transcription coactivator 1: important roles in neurodegenerative disorders

XUE Zhan-Cheng, WANG Chuang, WANG Qin-Wen, ZHANG Jun-Fang

School of Medicine, Ningbo University, Ningbo 315211, China； Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo 315211, China

Abstract

The cAMP-responsive element binding protein (CREB)-regulated transcription coactivator, CRTC (also known as transducer of regulated CREB, TORC), is identified as a potent modulator of cAMP response element (CRE)-driven gene transcription. The CRTC family consists of three members (CRTC1–3), among which the CRTC1 shows the highest expression in the brain. Several studies have demonstrated that the CRTC1 plays critical roles in neuronal dendritic growth, long-term synaptic plasticity, memory consolidation and reconsolidation etc., whereas dysfunction of CRTC1 is mainly involved in neurodegenerative disorders. In light of these findings, we aim to review recent research reports that indicate the CRTC1 dysfunction and its underlying mechanisms in the neurodegenerative disorders.

Key words: CREB-regulated transcription coactivator 1; cAMP-responsive element binding protein; CRE-driven gene transcription; neurodegenerative disorders; Alzheimer’s disease; Huntington’s disease

收稿日期：2014-12-23　　录用日期：2015-02-26

通讯作者：张俊芳　　E-mail: zhangjunfang@nbu.edu.cn

引用本文：

薛占成, 王闯, 王钦文, 张俊芳. CREB转录共激活因子1在神经退行性相关疾病中的研究进展[J]. 生理学报 2015; 67 (2): 155-162.

XUE Zhan-Cheng, WANG Chuang, WANG Qin-Wen, ZHANG Jun-Fang. CREB-regulated transcription coactivator 1: important roles in neurodegenerative disorders. Acta Physiol Sin 2015; 67 (2): 155-162 (in Chinese with English abstract).