Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases
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,...
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| Language: | English |
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Elsevier
2025-04-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725000825 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Antonio Cuadrado |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0920701655c94a28a7ea437f5c8b29aa |
| institution | DOAJ |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-0920701655c94a28a7ea437f5c8b29aa2025-08-20T03:00:07ZengElsevierRedox Biology2213-23172025-04-018110356910.1016/j.redox.2025.103569Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseasesAntonio Cuadrado0Eduardo Cazalla1Anders Bach2Boushra Bathish3Sharadha Dayalan Naidu4Gina M. DeNicola5Albena T. Dinkova-Kostova6Raquel Fernández-Ginés7Anna Grochot-Przeczek8John D. Hayes9Thomas W. Kensler10Rafael León11Karen T. Liby12Manuela G. López13Gina Manda14Akshatha Kalavathi Shivakumar15Henriikka Hakomäki16Jessica A. Moerland17Hozumi Motohashi18Ana I. Rojo19Gerasimos P. Sykiotis20Keiko Taguchi21Ángela M. Valverde22Masayuki Yamamoto23Anna-Liisa Levonen24Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Corresponding author. Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain.Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, DenmarkJacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UKJacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UKDepartment of Metabolism and Physiology, H. Lee. Moffitt Cancer Center, Tampa, FL, 33612, USAJacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UKDepartment of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandJacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UKTranslational Research Program, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USAInstituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), 28007, Madrid, SpainIndiana University School of Medicine, Department of Medicine, W. Walnut Street, Indianapolis, IN, 46202, USADepartment of Pharmacology, School of Medicine, Universidad Autónoma Madrid, Madrid, Spain; Instituto de Investigación Sanitario (IIS-IP), Hospital Universitario de La Princesa, Madrid, Spain; Instituto Teófilo Hernando, Madrid, SpainRadiobiology Laboratory, Victor Babes National Institute of Pathology, Bucharest, RomaniaA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandIndiana University School of Medicine, Department of Medicine, W. Walnut Street, Indianapolis, IN, 46202, USADepartment of Medical Biochemistry, Graduate School of Medicine Tohoku University, Sendai, Japan; Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Lausanne, SwitzerlandDepartment of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainIDAC, Tohoku University, Sendai, JapanLaboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan; Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, JapanInstituto de Investigaciones Biomédicas ''Sols-Morreale'' UAM-CSIC, Instituto de Investigación Sanitaria La Paz (IdiPaz), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, SpainDepartment of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, JapanA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland; Corresponding author. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio Campus, Neulaniementie 2, P.O. Box 1627, 70211, Kuopio, Finland.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.http://www.sciencedirect.com/science/article/pii/S2213231725000825KEAP1NRF2 diseasomeGSK-3β-TrCPDrug repurposing |
| spellingShingle | 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 Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases Redox Biology KEAP1 NRF2 diseasome GSK-3 β-TrCP Drug repurposing |
| title | Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases |
| title_full | Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases |
| title_fullStr | Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases |
| title_full_unstemmed | Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases |
| title_short | Health position paper and redox perspectives – Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases |
| title_sort | health position paper and redox perspectives bench to bedside transition for pharmacological regulation of nrf2 in noncommunicable diseases |
| topic | KEAP1 NRF2 diseasome GSK-3 β-TrCP Drug repurposing |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725000825 |
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