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

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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Redox Biology
Subjects:
KEAP1
NRF2 diseasome
GSK-3
β-TrCP
Drug repurposing
Online Access:http://www.sciencedirect.com/science/article/pii/S2213231725000825
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Summary: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.
ISSN:2213-2317

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