Keap1/Nrf2/ARE信号通路在中枢神经系统疾病中的研究进展  

Research Progress on the Role of Keap1 /Nrf2 /ARE Signaling Pathway in Central Nervous System Diseases

作　　者：李珊珊[1,2] 陈忠云[1,2] 李婧[1,2] 徐志伟[1,2] 杨旭[1,2] 

机构地区：[1]北京市航天中心医院 [2]北京大学航天临床医学院神经内科,100049

出　　处：《中国全科医学》2014年第30期3641-3644,共4页Chinese General Practice

基　　金：院级基金资助项目(YN201306)

摘　　要：Keap1/Nrf2/ARE信号通路是目前研究发现的最重要的抗氧化应激通路。NF-E2相关因子2(Nrf2)是自身抗氧化应激调节因子,生理条件下在细胞质中与kelch样ECH相关蛋白1(Keap1)结合,并不断地泛素化降解,无法进入细胞核发挥转录活性。当受到氧化应激、亲电子物质作用可使Keap1构象改变,Nrf2与Keap1解离后活化。活化后的Nrf2进入细胞核内与抗氧化反应元件(ARE)结合,启动下游Ⅱ相解毒酶、抗氧化蛋白类、泛素酶以及蛋白酶体的基因表达。Keap1/Nrf2/ARE信号通路通过调节这些下游基因的表达对脑血管疾病和神经退行性疾病起到保护作用,故而本文对Keap1/Nrf2/ARE信号通路在中枢神经系统疾病的作用作一综述。Recent studies have found that Keap1/Nrf2/ARE signaling pathway is the most important anti- oxidative stress pathway. Nrf2 is an anti- oxidative stress regulator,it unites with Keap1 in the cytoplasm under the physiological conditions,and degrades via ubiquitination,Nrf2 cannot enter the nucleus to perform transcriptional activity. The conformation of Keap1 can be changed by oxidative stress and electrophilic material,Nrf2 can be activated when it is disentangled from Keap1,the activated Nrf2 enters the nucleus and unites with ARE,and starts gene expression of downstream phase Ⅱ detoxifying enzymes,antioxidant enzymes,ubiquitin enzymes and proteasome. Keap1 /Nrf2 /ARE signaling pathway plays a protective role in cerebrovascular diseases and neurodegenerative diseases by regulating the expression of these downstream genes. This article reviews the role of Keap1 /Nrf2 /ARE signaling pathway in central nervous system diseases.

关 键 词：信号传导 神经系统疾病 氧化应激 

分 类 号：R743[医药卫生—神经病学与精神病学]