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

Humans NF-E2-Related Factor 2 / metabolism Kelch-Like ECH-Associated Protein 1 / metabolism Oxidative Stress Antioxidants / metabolism Inflammatory Bowel Diseases / drug therapy
NRF2/Keap1 pathway inflammatory bowel disease oxidative stress personalized medicine redox medicine

Journal

Trends in molecular medicine
ISSN: 1471-499X
Titre abrégé: Trends Mol Med
Pays: England
ID NLM: 100966035

Informations de publication

Date de publication:
10 2023
Historique:
received: 14 06 2023
revised: 14 07 2023
accepted: 17 07 2023
medline: 18 9 2023
pubmed: 10 8 2023
entrez: 9 8 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.molmed.2023.07.008 PMID: 37558549
pubmed: 37558549
pii: S1471-4914(23)00158-2
doi: 10.1016/j.molmed.2023.07.008
pii:
doi:

Substances chimiques

NF-E2-Related Factor 2 0
Kelch-Like ECH-Associated Protein 1 0
Antioxidants 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

830-842

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests S.G., A.R.B., R.R.F., R.G., R.K.W., H.v.G., G.D., and K.N.F. are supported by a research grant from Janssen Research & Development LLC. A.R.B. received speaker fees from AbbVie. R.K.W. acted as consultant for Takeda, received unrestricted research grants from Takeda, Johnson & Johnson, Tramedico, and Ferring and received speaker fees from MSD, AbbVie, and Janssen Pharmaceuticals. G.D. received research grants from Royal DSM, Takeda, and Janssen Pharmaceuticals and speaker fees from AbbVie, Pfizer, Takeda, and Janssen Pharmaceuticals.

Auteurs

Sem Geertsema (S)

Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: s.geertsema@umcg.nl.

Arno R Bourgonje (AR)

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.

Raphael R Fagundes (RR)

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

Ranko Gacesa (R)

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

Rinse K Weersma (RK)

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

Harry van Goor (H)

Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Giovanni E Mann (GE)

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.

Gerard Dijkstra (G)

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

Klaas N Faber (KN)

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

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The NRF2/Keap1 pathway as a therapeutic target...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Facteur-2 apparenté à NF-E2 › The NRF2/Keap1 pathway as a therapeutic target...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéine-1 de type kelch associée à ECH › The NRF2/Keap1 pathway as a therapeutic target...
questionsmedicales.fr › Phénomènes physiologiques › Stress physiologique › Stress oxydatif › The NRF2/Keap1 pathway as a therapeutic target...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Agents protecteurs › Antioxydants › The NRF2/Keap1 pathway as a therapeutic target...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › The NRF2/Keap1 pathway as a therapeutic target...