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.

中文翻译：

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在疾病中调节 NRF2：时机就是一切。


转录因子核因子红细胞 2 (NF-E2) 相关因子 2 (NRF2) 是氧化还原、代谢和蛋白质稳态的中心调节因子，与许多其他信号级联相互作用。尽管对 NRF2 信号传导复杂性的了解不断加深，但临床上只有一种靶向 NRF2 的治疗方法，即富马酸二甲酯，用于治疗多发性硬化症。新疗法的发现因 NRF2 水平根据生理和病理背景而显着变化这一事实而令人困惑。因此，对 NRF2 通路进行适当的定时和有针对性的操作对于制定有效的治疗方案至关重要。在这篇综述中，我们总结了 NRF2 的调控和下游目标。此外，我们还讨论了 NRF2 在癌症、神经退行性疾病、糖尿病以及心血管、肾脏和肝脏疾病中的作用，特别强调基于 NRF2 的治疗方法，包括那些已进入临床试验的治疗方法。