Abstract:
Nuclear factor erythroid 2-related factor 2 (Nrf2) functions as a central regulator in modulating the activities of diverse antioxidant enzymes, maintaining cellular redox balance, and responding to oxidative stress (OS). Kelch-like ECH-associated protein 1 (Keap1) serves as a principal negative modulator in controlling the expression of detoxification and antioxidant genes. It is widely accepted that OS plays a pivotal role in the pathogenesis of various diseases. When OS occurs, leading to inflammatory infiltration of neutrophils, increased secretion of proteases, and the generation of large quantities of reactive oxygen radicals (ROS). These ROS can oxidize or disrupt DNA, lipids, and proteins either directly or indirectly. They also cause gene mutations, lipid peroxidation, and protein denaturation, all of which can result in disease. The Keap1-Nrf2 signaling pathway regulates the balance between oxidants and antioxidants in vivo, maintains the stability of the intracellular environment, and promotes cell growth and repair. However, the antioxidant properties of the Keap1-Nrf2 signaling pathway are reduced in disease. This review overviews the mechanisms of OS generation, the biological properties of Keap1-Nrf2, and the regulatory role of its pathway in health and disease, to explore therapeutic strategies for the Keap1-Nrf2 signaling pathway in different diseases.
摘要:
核因子红系2相关因子2(Nrf2)在调节多种抗氧化酶的活性方面起着中枢调节因子的作用,维持细胞氧化还原平衡,并响应氧化应激(OS)。Kelch样ECH相关蛋白1(Keap1)是控制解毒和抗氧化基因表达的主要负调节剂。OS在各种疾病的发病机制中起着举足轻重的作用已被广泛接受。当操作系统发生时,导致中性粒细胞的炎症浸润,蛋白酶分泌增加,并产生大量的活性氧自由基(ROS)。这些ROS可以氧化或破坏DNA,脂质,和蛋白质直接或间接。它们还会导致基因突变,脂质过氧化,和蛋白质变性,所有这些都可能导致疾病。Keap1-Nrf2信号通路在体内调节氧化剂和抗氧化剂之间的平衡,维持细胞内环境的稳定,促进细胞生长和修复。然而,Keap1-Nrf2信号通路的抗氧化特性在疾病中降低。这篇综述概述了操作系统生成的机制,Keap1-Nrf2的生物学特性及其通路在健康和疾病中的调节作用,探讨Keap1-Nrf2信号通路在不同疾病中的治疗策略。