文献类型：期刊文献

中文题名：基于Keap1/Nrf2/ARE信号通路的天然产物在神经保护方面的研究进展

英文题名：Neuroprotection of Natural Products Based on Keap1/Nrf2/ARE Signaling Pathway:A Review

作者：刘圆圆[1,2];彭婷[3,4];姚娟[3,4,5];刘永琦[1,2]

第一作者：刘圆圆

机构：[1]甘肃中医药大学基础医学院,兰州730000;[2]敦煌医学与转化教育部重点实验室,兰州730000;[3]甘肃中医药大学药学院,兰州730000;[4]西北中藏药省部共建协同创新中心,兰州730000;[5]甘肃省中医药研究中心,兰州730000

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2023

卷号：29

期号：7

起止页码：262

中文期刊名：中国实验方剂学杂志

外文期刊名：Chinese Journal of Experimental Traditional Medical Formulae

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金青年基金项目(82104370);甘肃省自然科学基金项目(21JR1RA270);甘肃省中医药研究中心开放课题(zyzx-2020-17)。

语种：中文

中文关键词：Kelch样ECH相关蛋白1(Keap1)/核因子E_(2)相关因子2(Nrf2)/抗氧化反应元件(ARE);信号通路;神经退行性疾病;氧化应激;天然产物

外文关键词：Kelch-like ECH-associated protein 1(Keap1)/nuclear factor E_(2)-related factor 2(Nrf2)/antioxidant response element(ARE);signaling pathway;neurodegenerative disease;oxidative stress;natural products

摘要：阿尔茨海默病、帕金森病、多发性硬化等神经退行性疾病的病理表现为异常蛋白质的聚集和积累、小胶质细胞激活和线粒体功能障碍等,最终导致神经元结构或功能逐渐丧失,并随着时间的推移而恶化,这些病理过程与活性氧(ROS)的产生有关,ROS会引起氧化应激并破坏蛋白质、脂质和DNA,引发细胞和组织损伤。Kelch样ECH相关蛋白1(Keap1)/核因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)信号通路是维持机体氧化还原平衡、防御氧化应激损伤的主要机制,Nrf2通过与细胞质中Keap1的解离和核转移,激活ARE相关的一系列抗氧化基因的表达,以保护机体免受氧化损伤,因此Keap1/Nrf2/ARE信号通路激活剂的发现与研究对神经退行性疾病的防治具有重要意义。天然产物因有显著的生物活性、不良反应小等特点,是新药研发的宝库。研究表明,多种天然产物能够激活Keap1/Nrf2/ARE信号通路,发挥神经保护作用。根据天然产物的结构特点,可分为黄酮类、萜类及挥发油类、多酚类和苯丙素类等。该文概述了Keap1/Nrf2/ARE信号通路调节疾病的内在机制,并总结了基于该信号通路的天然产物在神经保护方面的研究进展,以期为研发防治神经退行性疾病的临床药物提供参考和依据。
The pathological manifestations of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis,are abnormal protein aggregation and accumulation,microglia activation,and mitochondrial dysfunction,which eventually lead to the gradual loss of neuronal structure or function and deteriorate over time. These pathological processes are related to the production of reactive oxygen species(ROS),which can cause oxidative stress and damage proteins,lipids,and DNA,leading to cell and tissue injuries. The Kelch-like ECH-associated protein 1(Keap1)/nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway is the main mechanism to maintain the redox balance of the body and defend against oxidative stress injury. Nrf2 activates the expression of a series of antioxidant genes related to ARE through the dissociation of Keap1 and nuclear transfer in the cytoplasm to protect the body from oxidative damage. Therefore,the discovery and study of the Keap1/Nrf2/ARE signaling pathway activator is of great significance for the prevention and treatment of neurodegenerative diseases. Because of the remarkable biological activity and slight side effects,natural products are a treasure trove for new drug research and development. Studies have shown that a variety of natural products can activate the Keap1/Nrf2/ARE signaling pathway and play a neuroprotective role. According to the structural characteristics,natural products can be divided into flavonoids,terpenoids,volatile oils,polyphenols,and phenylpropanoids. This study summarized the underlying mechanism of the Keap1/Nrf2/ARE signaling pathway in regulating diseases and reviewed the research progress on natural products based on this signaling pathway in neuroprotection to provide references for the development of clinical drugs for the prevention and treatment of neurodegenerative diseases.