Wang Luyao, Xu Rongyang, Huang Chengying, Yi Guozhong, Li Zhiyong, Zhang Huayang, Ye Rongxu, Qi Songtao, Huang Guanglong, Qu Shanqiang
Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
The Laboratory for Precision Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Gen Psychiatr. 2023 Oct 19;36(5):e101072. doi: 10.1136/gpsych-2023-101072. eCollection 2023.
Depression is a major contributor to poor global health and disability, with a recently increasing incidence. Although drug therapy is commonly used to treat depression, conventional antidepressant drugs have several disadvantages, including slow onset, low response rates and severe adverse effects. Therefore, developing effective therapies for depression remains challenging. Although various aetiological theories of depression exist, the underlying mechanisms of depression are complex, and further research is crucial. Moreover, oxidative stress (OS)-induced lipid peroxidation has been demonstrated to trigger ferroptosis. Both OS and ferroptosis are pivotal mechanisms implicated in the pathogenesis of neurological disorders, and investigation of the mediators involved in these processes has emerged as a prominent and active research direction. One previous study revealed that regulatory proteins involved in ferroptosis are implicated in the pathogenesis of depression, and antidepressant drugs could reverse depressive symptoms by inhibiting ferroptosis , suggesting an important role of ferroptosis in the pathogenesis of depression. Hence, our current comprehensive review offers an up-to-date perspective on the intricate mechanisms involved, specifically concerning ferroptosis and OS in the context of depression, along with promising prospects for using molecular mediators to target ferroptosis. We delineate the key targets of molecular mediators involved in OS and ferroptosis implicated in depression, most notably reactive oxygen species and iron overload. Considering the pivotal role of OS-induced ferroptosis in the pathogenesis of neurological disorders, delving deeper into the underlying subsequent mechanisms will contribute significantly to the identification of novel therapeutic targets for depression.
抑郁症是全球健康状况不佳和残疾的主要原因之一，其发病率最近呈上升趋势。尽管药物治疗常用于治疗抑郁症，但传统的抗抑郁药物有几个缺点，包括起效缓慢、有效率低和严重的副作用。因此，开发有效的抑郁症治疗方法仍然具有挑战性。虽然存在各种抑郁症的病因理论，但抑郁症的潜在机制很复杂，进一步的研究至关重要。此外，氧化应激（OS）诱导的脂质过氧化已被证明会引发铁死亡。OS和铁死亡都是神经疾病发病机制中的关键机制，对参与这些过程的介质的研究已成为一个突出且活跃的研究方向。先前的一项研究表明，参与铁死亡的调节蛋白与抑郁症的发病机制有关，抗抑郁药物可以通过抑制铁死亡来逆转抑郁症状，这表明铁死亡在抑郁症发病机制中起重要作用。因此，我们目前的综合综述提供了一个关于所涉及的复杂机制的最新观点，特别是关于抑郁症背景下的铁死亡和OS，以及使用分子介质靶向铁死亡的前景。我们阐述了参与抑郁症的OS和铁死亡的分子介质的关键靶点，最显著的是活性氧和铁过载。鉴于OS诱导的铁死亡在神经疾病发病机制中的关键作用，深入研究其潜在的后续机制将对确定抑郁症的新治疗靶点有很大帮助。
