Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases
Oxidative stress is a major component of cell damage and cell fat, and as such, it occupies a central position in the pathogenesis of metabolic disease. Nuclear factor-erythroid-derived 2-related factor 2 (Nrf2), a key transcription factor that coordinates expression of genes encoding antioxidant an...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2846 |
| _version_ | 1797474890211655680 |
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| author | Min-Ji Kim Jae-Han Jeon |
| author_facet | Min-Ji Kim Jae-Han Jeon |
| author_sort | Min-Ji Kim |
| collection | DOAJ |
| description | Oxidative stress is a major component of cell damage and cell fat, and as such, it occupies a central position in the pathogenesis of metabolic disease. Nuclear factor-erythroid-derived 2-related factor 2 (Nrf2), a key transcription factor that coordinates expression of genes encoding antioxidant and detoxifying enzymes, is regulated primarily by Kelch-like ECH-associated protein 1 (Keap1). However, involvement of the Keap1–Nrf2 pathway in tissue and organism homeostasis goes far beyond protection from cellular stress. In this review, we focus on evidence for Nrf2 pathway dysfunction during development of several metabolic/inflammatory disorders, including diabetes and diabetic complications, obesity, inflammatory bowel disease, and autoimmune diseases. We also review the beneficial role of current molecular Nrf2 agonists and summarize their use in ongoing clinical trials. We conclude that Nrf2 is a promising target for regulation of numerous diseases associated with oxidative stress and inflammation. However, more studies are needed to explore the role of Nrf2 in the pathogenesis of metabolic/inflammatory diseases and to review safety implications before therapeutic use in clinical practice. |
| first_indexed | 2024-03-09T20:36:27Z |
| format | Article |
| id | doaj.art-ecb646f672e2429fa823de4b368054e3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:36:27Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ecb646f672e2429fa823de4b368054e32023-11-23T23:10:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01235284610.3390/ijms23052846Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory DiseasesMin-Ji Kim0Jae-Han Jeon1Department of Endocrinology in Internal Medicine, Kyungpook National University Hospital, Daegu 41944, KoreaDepartment of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, KoreaOxidative stress is a major component of cell damage and cell fat, and as such, it occupies a central position in the pathogenesis of metabolic disease. Nuclear factor-erythroid-derived 2-related factor 2 (Nrf2), a key transcription factor that coordinates expression of genes encoding antioxidant and detoxifying enzymes, is regulated primarily by Kelch-like ECH-associated protein 1 (Keap1). However, involvement of the Keap1–Nrf2 pathway in tissue and organism homeostasis goes far beyond protection from cellular stress. In this review, we focus on evidence for Nrf2 pathway dysfunction during development of several metabolic/inflammatory disorders, including diabetes and diabetic complications, obesity, inflammatory bowel disease, and autoimmune diseases. We also review the beneficial role of current molecular Nrf2 agonists and summarize their use in ongoing clinical trials. We conclude that Nrf2 is a promising target for regulation of numerous diseases associated with oxidative stress and inflammation. However, more studies are needed to explore the role of Nrf2 in the pathogenesis of metabolic/inflammatory diseases and to review safety implications before therapeutic use in clinical practice.https://www.mdpi.com/1422-0067/23/5/2846Nrf2oxidative stressmetabolic diseaseinflammatory diseaseclinical trials |
| spellingShingle | Min-Ji Kim Jae-Han Jeon Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases International Journal of Molecular Sciences Nrf2 oxidative stress metabolic disease inflammatory disease clinical trials |
| title | Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases |
| title_full | Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases |
| title_fullStr | Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases |
| title_full_unstemmed | Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases |
| title_short | Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases |
| title_sort | recent advances in understanding nrf2 agonism and its potential clinical application to metabolic and inflammatory diseases |
| topic | Nrf2 oxidative stress metabolic disease inflammatory disease clinical trials |
| url | https://www.mdpi.com/1422-0067/23/5/2846 |
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