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Keap1-Nrf2信号通路在呼吸系统疾病治疗中的作用及靶向药物研究进展

The role of Keap1-Nrf2 signaling pathway in the treatment of respiratory diseases and the research progress on targeted drugs.

作者信息

Zhang Mengyang, Wang Jing, Liu Runze, Wang Qi, Qin Song, Chen Yuqin, Li Wenjun

机构信息

Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, Shandong, 266112, China.

Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, 264003, China.

出版信息

Heliyon. 2024 Sep 3;10(18):e37326. doi: 10.1016/j.heliyon.2024.e37326. eCollection 2024 Sep 30.

Abstract

Lungs are exposed to external oxidants from the environment as in harmful particles and smog, causing oxidative stress in the lungs and consequently respiratory ailment. The NF-E2-related factor 2 (Nrf2) is the one with transcriptional regulatory function, while its related protein Kelch-like ECH-associated protein 1 (Keap1) inhibits Nrf2 activity. Together, they form the Keap1-Nrf2 pathway, which regulates the body's defense against oxidative stress. This pathway has been shown to maintain cellular homeostasis during oxidative stressing, inflammation, oncogenesis, and apoptosis by coordinating the expression of cytoprotective genes and making it a potential therapeutic target for respiratory diseases. This paper summarizes this point in detail in Chapter 2. In addition, this article summarizes the current drug development and clinical research progress related to the Keap1-Nrf2 signaling pathway, with a focus on the potential of Nrf2 agonists in treating respiratory diseases. Overall, the article reviews the regulatory mechanisms of the Keap1-Nrf2 signaling pathway in respiratory diseases and the progress of targeted drug research, aiming to provide new insights for treatment.

摘要

肺部会暴露于环境中的外部氧化剂,如有害颗粒和烟雾中,这会导致肺部产生氧化应激,进而引发呼吸系统疾病。核因子E2相关因子2(Nrf2)具有转录调节功能,而其相关蛋白 Kelch样ECH相关蛋白1(Keap1)会抑制Nrf2的活性。它们共同构成了Keap1-Nrf2通路,该通路调节机体对氧化应激的防御。已证明该通路通过协调细胞保护基因的表达,在氧化应激、炎症、肿瘤发生和细胞凋亡过程中维持细胞稳态,使其成为呼吸系统疾病的潜在治疗靶点。本文在第2章中对此进行了详细总结。此外,本文还总结了与Keap1-Nrf2信号通路相关的当前药物研发和临床研究进展,重点关注Nrf2激动剂在治疗呼吸系统疾病方面的潜力。总体而言,本文综述了Keap1-Nrf2信号通路在呼吸系统疾病中的调节机制以及靶向药物研究进展,旨在为治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11414506/9ec2c114f2de/gr1.jpg

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