Antioxid Redox Signal. 2010 Dec 1;13(11):1623-6. doi: 10.1089/ars.2010.3301. Epub 2010 Aug 23.
The NF-E2-related factor-2 (Nrf2) is a transcription factor that is ubiquitously expressed at low levels in all human organs. As Nrf2 regulates a major cellular defense mechanism, tight regulation is crucial to maintain cellular homeostasis. Activation of this pathway is important in preventing human diseases, such as cancer, neurodegenerative disease, cardiovascular diseases, ischemia, diabetes, pulmonary fibrosis, and inflammatory diseases. Conversely, high constitutive levels of Nrf2 occur in many tumors or cancer cell lines. Moreover, overexpression of Nrf2 in cancer cells protects them from the cytotoxic effects of anticancer therapies, resulting in chemo- and/or radioresistance. Therefore, understanding Nrf2 regulation and identifying Nrf2 activators or inhibitors for disease prevention or as sensitizing agents during cancer therapy, respectively, will have a significant impact on human health. The growing interest in Nrf2 is reflected by an exponentially increasing number of annual publications on this topic. The present forum provides a comprehensive review on research conducted since the initial discovery of the Nrf2-Keap1 pathway in 1999, provides readers with insight into contemporary research in this field, and assesses current known biological functions of this pathway. Additionally, the forum will serve as an important resource for both graduate students and active researchers who are interested in the Nrf2 field.
核因子红细胞 2 相关因子 2（Nrf2）是一种转录因子，在所有人类器官中均低水平广泛表达。由于 Nrf2 调节主要的细胞防御机制，因此严格的调控对于维持细胞内稳态至关重要。激活这条通路对于预防人类疾病（如癌症、神经退行性疾病、心血管疾病、缺血、糖尿病、肺纤维化和炎症性疾病）非常重要。相反，许多肿瘤或癌细胞系中存在高组成性的 Nrf2 水平。此外，癌细胞中 Nrf2 的过表达可保护其免受抗癌治疗的细胞毒性作用，导致化疗和/或放疗耐药。因此，了解 Nrf2 的调控以及识别 Nrf2 激活剂或抑制剂，分别用于疾病预防或作为癌症治疗中的增敏剂，将对人类健康产生重大影响。对 Nrf2 的日益关注反映在该主题的年度出版物数量呈指数级增长上。本论坛提供了自 1999 年首次发现 Nrf2-Keap1 通路以来进行的研究的全面综述，为读者提供了对该领域当前研究的深入了解，并评估了该通路的当前已知生物学功能。此外，该论坛将为对 Nrf2 领域感兴趣的研究生和活跃研究人员提供重要资源。
