Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, Hubei, China.
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; The Research Center for Depression, Tongji Medical College, Huazhong University of Science, Wuhan, Hubei, China; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China; Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China.
Redox Biol. 2022 Dec;58:102522. doi: 10.1016/j.redox.2022.102522. Epub 2022 Oct 31.
The balance between oxidation and antioxidant is crucial for maintaining homeostasis. Once disrupted, it can lead to various pathological outcomes and diseases, such as depression. Oxidative stress can result in or aggravate a battery of pathological processes including mitochondrial dysfunction, neuroinflammation, autophagical disorder and ferroptosis, which have been found to be involved in the development of depression. Inhibition of oxidative stress and related pathological processes can help improve depression. In this regard, the nuclear factor erythroid 2-related factor 2 (Nrf2) in the antioxidant defense system may play a pivotal role. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damages, but also directly regulate the genes related to the above pathological processes to combat the corresponding alterations. Therefore, targeting Nrf2 has great potential for the treatment of depression. Activation of Nrf2 has antidepressant effect, but the specific mechanism remains to be elucidated. This article reviews the key role of Nrf2 in depression, focusing on the possible mechanisms of Nrf2 regulating oxidative stress and related pathological processes in depression treatment. Meanwhile, we summarize some natural and synthetic compounds targeting Nrf2 in depression therapy. All the above may provide new insights into targeting Nrf2 for the treatment of depression and provide a broad basis for clinical transformation.
氧化与抗氧化之间的平衡对于维持体内平衡至关重要。一旦这种平衡被打破，就可能导致各种病理后果和疾病，如抑郁症。氧化应激可导致或加重一系列病理过程，包括线粒体功能障碍、神经炎症、自噬障碍和铁死亡，这些过程已被发现与抑郁症的发展有关。抑制氧化应激和相关的病理过程有助于改善抑郁症。在这方面，抗氧化防御系统中的核因子红细胞 2 相关因子 2 (Nrf2) 可能发挥关键作用。Nrf2 的激活不仅可以调节一系列抗氧化基因的表达，从而减轻氧化应激及其损伤，还可以直接调节与上述病理过程相关的基因，以对抗相应的改变。因此，针对 Nrf2 具有治疗抑郁症的巨大潜力。Nrf2 的激活具有抗抑郁作用，但具体机制仍有待阐明。本文综述了 Nrf2 在抑郁症中的关键作用，重点讨论了 Nrf2 调节抑郁症治疗中氧化应激和相关病理过程的可能机制。同时，我们总结了一些针对 Nrf2 治疗抑郁症的天然和合成化合物。所有这些都可能为针对 Nrf2 治疗抑郁症提供新的思路，并为临床转化提供广泛的基础。
