Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213. United States.
Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282. United States.
CNS Neurol Disord Drug Targets. 2017;16(3):326-338. doi: 10.2174/1871527316666170102120211.
Central nervous system diseases are major health issues and are often associated with disability or death. Most central nervous system disorders are characterized by high levels of oxidative stress. Nuclear factor erythroid 2 related factor (Nrf2) is known for its ability to regulate the expression of a series of enzymes with antioxidative, prosurvival, and detoxification effects. Under basal conditions, Nrf2 forms a complex with Kelch-like ECH associated protein 1, leading to Nrf2 inactivation via ubiquitination and degradation. However, following exposure of Keap1 to oxidative stress, Nrf2 is released from Keap1, activated, and translocated into the nucleus. Upon nuclear entry, Nrf2 binds to antioxidant response elements (ARE), thereby inducing the expression of genes such as glutathione s-transferase, heme oxygenase 1, and NADPH quinine oxidoreductase 1. Many dietary phytochemicals have been reported to activate the protective Nrf2/ARE pathway. Here, we review the preventive and protective effects of dietary Nrf2 activators against CNS diseases, including stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease.
中枢神经系统疾病是重大健康问题，常导致残疾或死亡。大多数中枢神经系统疾病的特点是高水平的氧化应激。核因子红细胞 2 相关因子 (Nrf2) 以其调节具有抗氧化、生存促进和解毒作用的一系列酶的表达的能力而闻名。在基础条件下，Nrf2 与 Kelch 样 ECH 相关蛋白 1 形成复合物，导致 Nrf2 通过泛素化和降解失活。然而，在 Keap1 暴露于氧化应激后，Nrf2 从 Keap1 中释放出来，被激活并转位到细胞核中。进入细胞核后，Nrf2 与抗氧化反应元件 (ARE) 结合，从而诱导谷胱甘肽 S-转移酶、血红素加氧酶 1 和 NADPH 醌氧化还原酶 1 等基因的表达。已报道许多膳食植物化学物质可激活保护性 Nrf2/ARE 途径。在这里，我们综述了膳食 Nrf2 激活剂对包括中风、创伤性脑损伤、阿尔茨海默病和帕金森病在内的中枢神经系统疾病的预防和保护作用。
