The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China.
Department of Ophthalmology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Apoptosis. 2024 Feb;29(1-2):3-21. doi: 10.1007/s10495-023-01902-9. Epub 2023 Oct 17.
Ferroptosis, a mode of cell death that was recently identified in 2012, is driven by iron-dependent lipid peroxidation and distinct from other mechanisms of cell death such as autophagy and apoptosis. Ferroptosis has the unique features of disruptions in iron equilibrium, iron-induced lipid peroxidation, and the accumulation of glutamate-induced cellular toxicity. The regulation of ferroptosis mainly involves the iron, lipid, and amino acid metabolic pathways, which are controlled by system Xc, voltage-dependent anion channels, p53 and other pathways. Neurodegenerative diseases involve gradual neuronal loss predominantly within the central nervous system and are categorized into both sporadic and rare hereditary disorders. These diseases result in the progressive decline of specific neuron populations and their interconnections. Recent investigations have revealed a strong correlation between the manifestation and progression of neurodegenerative diseases and ferroptosis. The pharmacological modulation of ferroptosis, whether by induction or inhibition, exhibits promising prospects for therapeutic interventions for these diseases. This review aims to examine the literature on ferroptosis and its implications in various neurodegenerative diseases. We hope to offer novel insights into the potential therapies targeting ferroptosis in central nervous system neurodegenerative diseases. However, there are still limitations of this review. First, despite our efforts to maintain objectivity during our analysis, this review does not cover all the studies on ferroptosis and neurodegenerative diseases. Second, cell death in neurodegenerative diseases is not solely caused by ferroptosis. Future research should focus on the interplay of different cell death mechanisms to better elucidate the specific disease pathogenesis.
铁死亡是一种于 2012 年新发现的细胞死亡方式，它由铁依赖性脂质过氧化驱动，与自噬和细胞凋亡等其他细胞死亡机制不同。铁死亡具有铁平衡破坏、铁诱导的脂质过氧化和谷氨酸诱导的细胞毒性积累等独特特征。铁死亡的调节主要涉及铁、脂质和氨基酸代谢途径，这些途径受系统 Xc、电压依赖性阴离子通道、p53 等途径的控制。神经退行性疾病涉及中枢神经系统内的神经元逐渐丧失，分为散发性和罕见遗传性疾病。这些疾病导致特定神经元群体及其相互连接的逐渐衰退。最近的研究表明，神经退行性疾病的表现和进展与铁死亡之间存在很强的相关性。铁死亡的药理学调节，无论是诱导还是抑制，都为这些疾病的治疗干预提供了有希望的前景。本综述旨在探讨铁死亡及其在各种神经退行性疾病中的意义的文献。我们希望为针对中枢神经系统神经退行性疾病中铁死亡的潜在治疗方法提供新的见解。然而，本综述仍然存在一些局限性。首先，尽管我们在分析过程中努力保持客观性，但本综述并未涵盖所有关于铁死亡和神经退行性疾病的研究。其次，神经退行性疾病中的细胞死亡不仅仅是由铁死亡引起的。未来的研究应侧重于不同细胞死亡机制的相互作用，以更好地阐明特定疾病的发病机制。
