Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
Department of Family Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan.
Cells. 2022 Nov 29;11(23):3829. doi: 10.3390/cells11233829.
Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation. The mechanisms of ferroptosis inhibitors enhance antioxidative capacity to counter the oxidative stress from lipid peroxidation, such as through the system x/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis and the coenzyme Q10 (CoQ10)/FSP1 pathway. Another means to reduce ferroptosis is with iron chelators. To date, there is no disease-modifying therapy to cure or slow PD progression, and a recent topic of research seeks to intervene with the development of PD via regulation of ferroptosis. In this review, we provide a discussion of different cell death pathways, the molecular mechanisms of ferroptosis, the role of ferroptosis in blood-brain barrier damage, updates on PD studies in ferroptosis, and the latest progress of pharmacological agents targeting ferroptosis for the intervention of PD in clinical trials.
帕金森病（PD）是第二常见的神经退行性疾病。患有 PD 的人多巴胺能神经元进行性丧失的特征性病理学与铁积累有关，并被认为部分是由新的细胞死亡途径铁死亡驱动的。铁死亡是一种独特的细胞死亡方式，由铁依赖性磷脂过氧化介导。铁死亡抑制剂的作用机制是通过系统 x/谷胱甘肽 (GSH)/谷胱甘肽过氧化物酶 4 (GPX4) 轴和辅酶 Q10 (CoQ10)/FSP1 途径增强抗氧化能力来对抗脂质过氧化引起的氧化应激。减少铁死亡的另一种方法是使用铁螯合剂。迄今为止，尚无治愈或减缓 PD 进展的疾病修正疗法，最近的研究主题是通过调节铁死亡来干预 PD 的发展。在这篇综述中，我们讨论了不同的细胞死亡途径、铁死亡的分子机制、铁死亡在血脑屏障损伤中的作用、铁死亡在 PD 研究中的最新进展以及针对铁死亡的药理学药物在临床试验中干预 PD 的最新进展。
