铁死亡调控机制及其在帕金森病中的研究进展

Mechanisms of ferroptosis and its involvement in Parkinson's disease

铁死亡是一种新型的细胞程序性死亡方式,其形态、生化特征及作用机制均不同于凋亡、自噬、坏死、焦亡等已知的细胞死亡形式。铁死亡的调控机制主要涉及铁代谢、氨基酸代谢及脂质代谢。已有研究发现铁死亡在神经、肿瘤、缺血再灌注损伤等疾病的发生发展中起关键作用。帕金森病(Parkinson's disease, PD)是中枢神经系统最常见的神经退行性疾病之一,其病因及发病机制尚未阐明。近期研究发现, PD患者中脑处具有高铁、低还原型谷胱甘肽及高过氧化脂质等特点,提示PD发病机制与铁死亡密切相关。在PD中,一些铁死亡抑制剂表现出缓解疾病的能力,其中一种铁离子螯合剂已进入临床试验阶段。本文系统总结铁死亡的主要调控机制并梳理其与PD的联系,为治疗PD提供新的潜在靶点。

Ferroptosis is a novel type of regulated cell death with morphology, biochemistry and mechanisms differing from traditional cell death types such as apoptosis, necrosis and pyroptosis. The regulatory mechanisms of ferroptosis mainly involve iron metabolism, amino acid metabolism and lipid metabolism. It has been found that ferroptosis plays a key role in the pathogenesis of diseases including neurodegenerative diseases, malignant tumors and ischemic reperfusion injury. Parkinson’s disease(PD) is one of the most common neurodegenerative diseases and its etiology and pathogenesis remains unclear. Recent studies revealed that ferroptosis might be involved in the pathogenesis of PD, as evidenced by high iron content, depletion of reduced form of glutathione and elevated levels of lipid peroxides detectable in the midbrain of PD patients. Both in vitro and in vivo models of PD have shown that some ferroptosis inhibitors have the ability of attenuating the symptoms and one iron chelator is undergoing a clinic trial. We here summarize the mechanisms of ferroptosis and its association with PD, in an effort to suggest potential novel targets for therapies of PD.