转录因子NRF2在阿尔茨海默病中的作用及治疗研究  

Research on the role and treatment of transcription factor NRF2 in Alzheimer’s disease

作　　者：邓磊 张俊丽 韩发彬 DENG Lei;ZHANG Jun-Li;HAN Fa-Bin(The Translational Research Laboratory for Stem Cell and Traditional Chinese Medicine,Innovative Institute of Chinese Medicine and Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东中医药大学中医药创新研究院,干细胞与中医药转化研究实验室,济南250355

出　　处：《生命科学》2022年第9期1090-1100,共11页Chinese Bulletin of Life Sciences

基　　金：山东省自然科学基金项目(ZR2019ZD39);济南市5150项目(JN2018-5150-HFB)。

摘　　要：阿尔茨海默病(Alzheimer’s disease, AD)是一种常见的神经退行性疾病。越来越多的证据表明氧化应激在AD的发生及发展中起着关键作用。核因子E2相关因子2 (nuclear factor E2-related factor 2, NRF2)是一种转录因子,在机体抗氧化中起着重要作用,其通过与抗氧化响应元件(antioxidant response element,ARE)结合,激活下游的NRF2/ARE依赖性基因并发挥调控氧化应激的作用。NRF2的激活在AD中可增强抗氧化能力,并在AD病理改变的多个方面起到关键作用,包括Aβ沉积、Tau磷酸化、神经炎症和线粒体损伤等。大量证据表明,在多种AD模型中NRF2的激活可明显延缓AD病程,改善认知功能障碍。本文对NRF2在AD中的作用及相关药物的研究进展进行综述,以期为AD的治疗提供新思路。Alzheimer’s disease(AD) is a common neurodegenerative disease, and the increasing evidence suggests that oxidative stress plays a key role in the occurrence and development of AD. Nuclear factor E2-related factor 2(NRF2) is a transcription factor which is crucial in antioxidant effects. NRF2 regulates oxidative stress by binding to antioxidant response element(ARE) to activate downstream NRF2/ARE-dependent genes. Furthermore, the activation of NRF2 could enhance the antioxidant capacity in AD and plays a key role in multiple aspects of AD pathological changes, including Aβ deposition, Tau phosphorylation, neuroinflammation and mitochondrial dysfunction. Extensive experimental evidence has shown that the activation of NRF2 could significantly alleviate the pathological progression and improve the cognitive dysfunction in various AD models. Therefore, this article reviews the roles and drugs related to NRF2 in AD, in order to provide new ideas for the treatment of AD.

关 键 词：阿尔茨海默病 NRF2 氧化应激 AΒ TAU NRF2激动剂 

分 类 号：R749.16[医药卫生—神经病学与精神病学]