Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Italian National Institute of Health, 00161 Rome, Italy.
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, 00161 Rome, Italy.
Molecules. 2020 Nov 23;25(22):5474. doi: 10.3390/molecules25225474.
Inflammation is a key driver in many pathological conditions such as allergy, cancer, Alzheimer's disease, and many others, and the current state of available drugs prompted researchers to explore new therapeutic targets. In this context, accumulating evidence indicates that the transcription factor Nrf2 plays a pivotal role controlling the expression of antioxidant genes that ultimately exert anti-inflammatory functions. Nrf2 and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH- associated protein 1 (Keap1), play a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Interestingly, Nrf2 is proved to contribute to the regulation of the heme oxygenase-1 (HO-1) axis, which is a potent anti-inflammatory target. Recent studies showed a connection between the Nrf2/antioxidant response element (ARE) system and the expression of inflammatory mediators, NF-κB pathway and macrophage metabolism. This suggests a new strategy for designing chemical agents as modulators of Nrf2 dependent pathways to target the immune response. Therefore, the present review will examine the relationship between Nrf2 signaling and the inflammation as well as possible approaches for the therapeutic modulation of this pathway.
炎症是许多病理状况的关键驱动因素，如过敏、癌症、阿尔茨海默病等，目前可用药物的状况促使研究人员探索新的治疗靶点。在这种情况下，越来越多的证据表明，转录因子 Nrf2 在控制抗氧化基因的表达方面起着关键作用，这些基因最终发挥抗炎作用。Nrf2 及其主要的负调节剂 E3 连接酶衔接蛋白 Kelch-like ECH- associated protein 1（Keap1）在维持细胞内氧化还原稳态和调节炎症中起着核心作用。有趣的是，Nrf2 被证明有助于血红素加氧酶-1（HO-1）轴的调节，HO-1 轴是一个强大的抗炎靶点。最近的研究表明，Nrf2/抗氧化反应元件（ARE）系统与炎症介质、NF-κB 通路和巨噬细胞代谢的表达之间存在联系。这表明了一种新的策略，即设计化学剂作为 Nrf2 依赖途径的调节剂，以靶向免疫反应。因此，本综述将探讨 Nrf2 信号通路与炎症之间的关系，以及对该通路进行治疗性调节的可能方法。
