《生命科学》 2022, 34(9): 1090-1100

转录因子NRF2在阿尔茨海默病中的作用及治疗研究

邓　磊 , 张俊丽 , 韩发彬^*

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

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。

通讯作者：韩发彬 , Email:fhan2013@126.com

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

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

Abstract:

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.

Communication Author：HAN Fa-Bin , Email:fhan2013@126.com