NRF2/Keap1 通路作为炎症性肠病的治疗靶点。

The NRF2/Keap1 pathway as a therapeutic target in inflammatory bowel disease.

机构信息

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Trends Mol Med. 2023 Oct;29(10):830-842. doi: 10.1016/j.molmed.2023.07.008. Epub 2023 Aug 7.

DOI:10.1016/j.molmed.2023.07.008

PMID:37558549

Abstract

Oxidative stress (OS) is an important pathophysiological mechanism in inflammatory bowel disease (IBD). However, clinical trials investigating compounds directly targeting OS in IBD yielded mixed results. The NRF2 (nuclear factor erythroid 2-related factor 2)/Keap1 (Kelch-like ECH-associated protein 1) pathway orchestrates cellular responses to OS, and dysregulation of this pathway has been implicated in IBD. Activation of the NRF2/Keap1 pathway may enhance antioxidant responses. Although this approach could help to attenuate OS and potentially improve clinical outcomes, an overview of human evidence for modulating the NRF2/Keap1 axis and more recent developments in IBD is lacking. This review explores the NRF2/Keap1 pathway as potential therapeutic target in IBD and presents compounds activating this pathway for future clinical applications.

摘要

氧化应激（OS）是炎症性肠病（IBD）的重要病理生理机制。然而，针对 IBD 中 OS 的直接作用化合物的临床试验结果喜忧参半。NRF2（核因子红细胞 2 相关因子 2）/Keap1（Kelch 样 ECH 相关蛋白 1）途径协调细胞对 OS 的反应，该途径的失调与 IBD 有关。NRF2/Keap1 途径的激活可能增强抗氧化反应。尽管这种方法有助于减轻 OS 并可能改善临床结局，但缺乏调节 NRF2/Keap1 轴的人体证据概述和 IBD 的最新进展。这篇综述探讨了 NRF2/Keap1 途径作为 IBD 的潜在治疗靶点，并提出了激活该途径的化合物，以供未来的临床应用。