Yan Ruihan, Lin Bingyi, Jin Wenwei, Tang Ling, Hu Shuming, Cai Rong
Department of Biochemistry & Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Antioxidants (Basel). 2023 Sep 8;12(9):1739. doi: 10.3390/antiox12091739.
Ferroptosis is an iron-dependent and lipid peroxidation-driven cell death cascade, occurring when there is an imbalance of redox homeostasis in the cell. Nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) is key for cellular antioxidant responses, which promotes downstream genes transcription by binding to their antioxidant response elements (AREs). Numerous studies suggest that NRF2 assumes an extremely important role in the regulation of ferroptosis, for its various functions in iron, lipid, and amino acid metabolism, and so on. Many pathological states are relevant to ferroptosis. Abnormal suppression of ferroptosis is found in many cases of cancer, promoting their progression and metastasis. While during tissue damages, ferroptosis is recurrently promoted, resulting in a large number of cell deaths and even dysfunctions of the corresponding organs. Therefore, targeting NRF2-related signaling pathways, to induce or inhibit ferroptosis, has become a great potential therapy for combating cancers, as well as preventing neurodegenerative and ischemic diseases. In this review, a brief overview of the research process of ferroptosis over the past decade will be presented. In particular, the mechanisms of ferroptosis and a focus on the regulation of ferroptosis by NRF2 will be discussed. Finally, the review will briefly list some clinical applications of targeting the NRF2 signaling pathway in the treatment of diseases.
铁死亡是一种铁依赖性且由脂质过氧化驱动的细胞死亡级联反应，当细胞内氧化还原稳态失衡时就会发生。核因子红细胞2相关因子2（NFE2L2，也称为NRF2）是细胞抗氧化反应的关键，它通过与下游基因的抗氧化反应元件（ARE）结合来促进这些基因的转录。大量研究表明，NRF2在铁死亡的调控中发挥着极其重要的作用，这源于它在铁、脂质和氨基酸代谢等方面的多种功能。许多病理状态都与铁死亡相关。在许多癌症病例中都发现铁死亡受到异常抑制，从而促进了癌症的进展和转移。而在组织损伤期间，铁死亡会反复被促进，导致大量细胞死亡甚至相应器官功能障碍。因此，靶向NRF2相关信号通路以诱导或抑制铁死亡，已成为对抗癌症以及预防神经退行性疾病和缺血性疾病的一种极具潜力的治疗方法。在这篇综述中，将简要概述过去十年铁死亡的研究历程。特别地，将讨论铁死亡的机制以及对NRF2调控铁死亡的关注。最后，该综述将简要列举一些靶向NRF2信号通路在疾病治疗中的临床应用。
