Instituto de Investigaciones Biomédicas "Alberto Sols" UAM-CSIC, Instituto de Investigación Sanitaria La Paz (IdiPaz) and Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Madrid, Spain.
Oxid Med Cell Longev. 2019 Jul 14;2019:9372182. doi: 10.1155/2019/9372182. eCollection 2019.
The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) triggers the first line of homeostatic responses against a plethora of environmental or endogenous deviations in redox metabolism, proteostasis, inflammation, etc. Therefore, pharmacological activation of NRF2 is a promising therapeutic approach for several chronic diseases that are underlined by oxidative stress and inflammation, such as neurodegenerative, cardiovascular, and metabolic diseases. A particular case is cancer, where NRF2 confers a survival advantage to constituted tumors, and therefore, NRF2 inhibition is desired. This review describes the electrophilic and nonelectrophilic NRF2 activators with clinical projection in various chronic diseases. We also analyze the status of NRF2 inhibitors, which at this time provide proof of concept for blocking NRF2 activity in cancer therapy.
转录因子 NRF2（红细胞生成素相关因子 2 的核因子）触发了针对氧化还原代谢、蛋白质稳定、炎症等方面的大量环境或内源性偏差的第一道稳态反应。因此，NRF2 的药理学激活是治疗多种慢性疾病的有前途的方法，这些疾病的特点是氧化应激和炎症，如神经退行性疾病、心血管疾病和代谢疾病。一个特殊的例子是癌症，其中 NRF2 赋予构成肿瘤生存优势，因此需要抑制 NRF2。本综述描述了具有各种慢性疾病临床前景的亲电和非亲电 NRF2 激活剂。我们还分析了 NRF2 抑制剂的现状，目前它们为在癌症治疗中阻断 NRF2 活性提供了概念验证。
