Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases

Antonio Cuadrado; Eduardo Cazalla; Anders Bach; Boushra Bathish; Sharadha Dayalan Naidu; Gina M DeNicola; Albena T Dinkova-Kostova; Raquel Fernández-Ginés; Anna Grochot-Przeczek; John D Hayes; Thomas W Kensler; Rafael León; Karen T Liby; Manuela G López; Gina Manda; Akshatha Kalavathi Shivakumar; Henriikka Hakomäki; Jessica A Moerland; Hozumi Motohashi; Ana I Rojo; Gerasimos P Sykiotis; Keiko Taguchi; Ángela M Valverde; Masayuki Yamamoto; Anna-Liisa Levonen

doi:10.1016/j.redox.2025.103569

Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases

Antonio Cuadrado, Eduardo Cazalla, Anders Bach, Boushra Bathish, Sharadha Dayalan Naidu, Gina M DeNicola, Albena T Dinkova-Kostova, Raquel Fernández-Ginés, Anna Grochot-Przeczek, John D Hayes, Thomas W Kensler, Rafael León, Karen T Liby, Manuela G López, Gina Manda, Akshatha Kalavathi Shivakumar, Henriikka Hakomäki, Jessica A Moerland, Hozumi Motohashi, Ana I RojoGerasimos P Sykiotis, Keiko Taguchi, Ángela M Valverde, Masayuki Yamamoto, Anna-Liisa Levonen

Medicinalkemi

Publikation: Bidrag til tidsskrift › Review › peer review

1 Citationer (Scopus)

2 Downloads (Pure)

Abstract

Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.

Originalsprog	Engelsk
Artikelnummer	103569
Tidsskrift	Redox Biology
Vol/bind	81
Antal sider	40
ISSN	2213-2317
DOI	https://doi.org/10.1016/j.redox.2025.103569
Status	Udgivet - 2025

Bibliografisk note

Adgang til dokumentet

10.1016/j.redox.2025.103569Licens: CC BY-NC-ND

FulltextForlagets udgivne version, 10,5 MBLicens: CC BY-NC-ND

Citationsformater

Cuadrado, A., Cazalla, E., Bach, A., Bathish, B., Naidu, S. D., DeNicola, G. M., Dinkova-Kostova, A. T., Fernández-Ginés, R., Grochot-Przeczek, A., Hayes, J. D., Kensler, T. W., León, R., Liby, K. T., López, M. G., Manda, G., Shivakumar, A. K., Hakomäki, H., Moerland, J. A., Motohashi, H., ... Levonen, A.-L. (2025). Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases. Redox Biology, 81, Artikel 103569. https://doi.org/10.1016/j.redox.2025.103569

Cuadrado, A, Cazalla, E, Bach, A, Bathish, B, Naidu, SD, DeNicola, GM, Dinkova-Kostova, AT, Fernández-Ginés, R, Grochot-Przeczek, A, Hayes, JD, Kensler, TW, León, R, Liby, KT, López, MG, Manda, G, Shivakumar, AK, Hakomäki, H, Moerland, JA, Motohashi, H, Rojo, AI, Sykiotis, GP, Taguchi, K, Valverde, ÁM, Yamamoto, M & Levonen, A-L 2025, 'Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases', Redox Biology, bind 81, 103569. https://doi.org/10.1016/j.redox.2025.103569

@article{7fb60e3b8dc44366a3125fe09dcbdd6b,

title = "Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases",

abstract = "Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.",

author = "Antonio Cuadrado and Eduardo Cazalla and Anders Bach and Boushra Bathish and Naidu, {Sharadha Dayalan} and DeNicola, {Gina M} and Dinkova-Kostova, {Albena T} and Raquel Fern{\'a}ndez-Gin{\'e}s and Anna Grochot-Przeczek and Hayes, {John D} and Kensler, {Thomas W} and Rafael Le{\'o}n and Liby, {Karen T} and L{\'o}pez, {Manuela G} and Gina Manda and Shivakumar, {Akshatha Kalavathi} and Henriikka Hakom{\"a}ki and Moerland, {Jessica A} and Hozumi Motohashi and Rojo, {Ana I} and Sykiotis, {Gerasimos P} and Keiko Taguchi and Valverde, {{\'A}ngela M} and Masayuki Yamamoto and Anna-Liisa Levonen",

year = "2025",

doi = "10.1016/j.redox.2025.103569",

language = "English",

volume = "81",

journal = "Redox Biology",

issn = "2213-2317",

publisher = "Elsevier",

}

TY - JOUR

T1 - Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases

AU - Cuadrado, Antonio

AU - Cazalla, Eduardo

AU - Bach, Anders

AU - Bathish, Boushra

AU - Naidu, Sharadha Dayalan

AU - DeNicola, Gina M

AU - Dinkova-Kostova, Albena T

AU - Fernández-Ginés, Raquel

AU - Grochot-Przeczek, Anna

AU - Hayes, John D

AU - Kensler, Thomas W

AU - León, Rafael

AU - Liby, Karen T

AU - López, Manuela G

AU - Manda, Gina

AU - Shivakumar, Akshatha Kalavathi

AU - Hakomäki, Henriikka

AU - Moerland, Jessica A

AU - Motohashi, Hozumi

AU - Rojo, Ana I

AU - Sykiotis, Gerasimos P

AU - Taguchi, Keiko

AU - Valverde, Ángela M

AU - Yamamoto, Masayuki

AU - Levonen, Anna-Liisa

PY - 2025

Y1 - 2025

N2 - Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.

AB - Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.

U2 - 10.1016/j.redox.2025.103569

DO - 10.1016/j.redox.2025.103569

M3 - Review

C2 - 40059038

SN - 2213-2317

VL - 81

JO - Redox Biology

JF - Redox Biology

M1 - 103569

ER -