转录因子Nrf2的神经保护作用及其机制

摘要/Abstract

摘要： NF-E2 相关因子2(Nrf2),感受体内反应活性氧(Reactive oxygen species, ROS)变化后,与体内的锚定蛋白Keap1解聚,发生核转位并调控下游多种抗氧化应激蛋白,解毒酶及转运体基因的表达,参与抗氧化应激生理及病理过程。目前,许多研究发现,Nrf2转录调控的下游靶基因可以对抗由脑中风氧化应激引起的神经系统病变,阿尔茨海默病(Alzheimer's disease), 帕金森病(Parkinson's disease),侧索硬化(Amyotrophic lateral sclerosis,ALS)。本文对近年来Nrf2在神经保护方面的作用及其机制,以及Nrf2作为药物治疗靶点治疗神经退行性病变的最新研究成果进行总结。

关键词: 抗氧化应激, Nrf2, 神经保护, Keap1, 抗氧化反应元件ARE

Abstract: Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor, which sensitive to the oxidative stress and electrophiles, translocation to nucleus after dissociation with Keap1, induce expression of a variety of cytoprotective and detoxification genes. Several of the genes which regulated by Nrf2 have been illustrated in prevention from neurodegenerative conditions. Work from several laboratories has implicated the potential for Nrf2-mediated transcription to protect conditions such as hypoxia, ischemic-reperfusion,Alzhemier's disease, Parkinson's disease and Amyotrophic lateral sclerosis, resulting from mechanisms involving oxidative stress. Nrf2 may be notable in fighting conditions with variable causes and etiologies. Therefore, we review the current literature that imply Nrf2 may be a crucial therapeutic target for neuronal system disease, as well as experiments that uncover potential mechanisms of protection.

Key words: Oxidative stress, Nrf2, Neuroprotection, Keap1, Antioxidant-responsive element

中图分类号:

曹杉, 周淦, 彭向东, 阳国平, 周宏灏. 转录因子Nrf2的神经保护作用及其机制[J]. 中国临床药理学与治疗学, 2013, 18(6): 696-704.

CAO Shan, ZHOU Gan, PENG Xiang-dong, YANG Guo-ping, ZHOU Hong-hao. Role of Nrf2 in neuroprotection and its mechanisms[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(6): 696-704.

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