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

Sem Geertsema; Arno R Bourgonje; Raphael R Fagundes; Ranko Gacesa; Rinse K Weersma; Harry van Goor; Giovanni E Mann; Gerard Dijkstra; Klaas N Faber

doi:10.1016/j.molmed.2023.07.008

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

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

Authors

Sem Geertsema¹, Arno R Bourgonje², Raphael R Fagundes³, Ranko Gacesa³, Rinse K Weersma³, Harry van Goor⁴, Giovanni E Mann⁵, Gerard Dijkstra³, Klaas N Faber³

Affiliations

¹ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: s.geertsema@umcg.nl.
² 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. Electronic address: a.r.bourgonje@umcg.nl.
³ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴ Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁵ King's British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK.

PMID: 37558549
DOI: 10.1016/j.molmed.2023.07.008

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.

Keywords: NRF2/Keap1 pathway; inflammatory bowel disease; oxidative stress; personalized medicine; redox medicine.

Publication types

Review

MeSH terms

Antioxidants / metabolism
Humans
Inflammatory Bowel Diseases* / drug therapy
Inflammatory Bowel Diseases* / etiology
Kelch-Like ECH-Associated Protein 1 / metabolism
NF-E2-Related Factor 2* / metabolism
Oxidative Stress

Substances

NF-E2-Related Factor 2
Kelch-Like ECH-Associated Protein 1
Antioxidants