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

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

^*Corresponding author voor dit werk

Onderzoeksoutput › peer review

48 Citaten (Scopus)

385 Downloads (Pure)

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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.

Originele taal-2	English
Pagina's (van-tot)	830-842
Aantal pagina's	13
Tijdschrift	Trends in Molecular Medicine
Volume	29
Nummer van het tijdschrift	10
Vroegere onlinedatum	7-aug.-2023
DOI's	https://doi.org/10.1016/j.molmed.2023.07.008
Status	Published - okt.-2023

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10.1016/j.molmed.2023.07.008

The NRF2/Keap1 pathway as a therapeutic target in inflammatory bowel diseaseFinal publisher's version, 1,68 MBLicentie: Taverne

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@article{98a4e62a79ef4d3bbb435f454709a25e,

title = "The NRF2/Keap1 pathway as a therapeutic target in inflammatory bowel disease",

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

author = "Sem Geertsema and Bourgonje, {Arno R.} and Fagundes, {Raphael R.} and Ranko Gacesa and Weersma, {Rinse K.} and {van Goor}, Harry and Mann, {Giovanni E.} and Gerard Dijkstra and Faber, {Klaas N.}",

year = "2023",

month = oct,

doi = "10.1016/j.molmed.2023.07.008",

language = "English",

volume = "29",

pages = "830--842",

journal = "Trends in Molecular Medicine",

issn = "1471-4914",

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}

TY - JOUR

T1 - The NRF2/Keap1 pathway as a therapeutic target in inflammatory bowel disease

AU - Geertsema, Sem

AU - Bourgonje, Arno R.

AU - Fagundes, Raphael R.

AU - Gacesa, Ranko

AU - Weersma, Rinse K.

AU - van Goor, Harry

AU - Mann, Giovanni E.

AU - Dijkstra, Gerard

AU - Faber, Klaas N.

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

KW - Humans

KW - NF-E2-Related Factor 2/metabolism

KW - Kelch-Like ECH-Associated Protein 1/metabolism

KW - Oxidative Stress

KW - Antioxidants/metabolism

KW - Inflammatory Bowel Diseases/drug therapy

U2 - 10.1016/j.molmed.2023.07.008

DO - 10.1016/j.molmed.2023.07.008

M3 - Review article

C2 - 37558549

SN - 1471-4914

VL - 29

SP - 830

EP - 842

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

IS - 10

ER -

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

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