Modulating NRF2 in Disease: Timing Is Everything
Autor: | Matthew Dodson, Eli Chapman, Cody J. Schmidlin, Aram B. Cholanians, Donna D. Zhang, Montserrat Rojo de la Vega |
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Rok vydání: | 2019 |
Předmět: |
Pharmacology
NF-E2-Related Factor 2 business.industry Multiple sclerosis Neurodegeneration Regulator Cancer Context (language use) Disease respiratory system Toxicology medicine.disease Bioinformatics digestive system environment and public health KEAP1 Article medicine Animals Humans business Transcription factor Signal Transduction |
Zdroj: | Annual Review of Pharmacology and Toxicology. 59:555-575 |
ISSN: | 1545-4304 0362-1642 |
Popis: | The transcription factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) is a central regulator of redox, metabolic, and protein homeostasis that intersects with many other signaling cascades. Although the understanding of the complex nature of NRF2 signaling continues to grow, there is only one therapeutic targeting NRF2 for clinical use, dimethyl fumarate, used for the treatment of multiple sclerosis. The discovery of new therapies is confounded by the fact that NRF2 levels vary significantly depending on physiological and pathological context. Thus, properly timed and targeted manipulation of the NRF2 pathway is critical in creating effective therapeutic regimens. In this review, we summarize the regulation and downstream targets of NRF2. Furthermore, we discuss the role of NRF2 in cancer, neurodegeneration, and diabetes as well as cardiovascular, kidney, and liver disease, with a special emphasis on NRF2-based therapeutics, including those that have made it into clinical trials. |
Databáze: | OpenAIRE |
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