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

Trends Mol Med. 2023 Aug 7:S1471-4914(23)00158-2. doi: 10.1016/j.molmed.2023.07.008. Online ahead of print.ABSTRACTOxidative 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.PMID:37558549 | DOI:10.1016/j.molmed.2023.07.008

Source: Trends in Molecular Medicine - August 9, 2023 Category: Molecular Biology Authors: Sem Geertsema Arno R Bourgonje Raphael R Fagundes Ranko Gacesa Rinse K Weersma Harry van Goor Giovanni E Mann Gerard Dijkstra Klaas N Faber Source Type: research