Zhang Guimei, Zhang Yaru, Shen Yanxin, Wang Yongchun, Zhao Meng, Sun Li
Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China.
Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
J Alzheimers Dis. 2021;80(3):907-925. doi: 10.3233/JAD-201369.
Alzheimer's disease (AD) is the most prevalent cause of dementia, accounting for approximately 60%-80%of all cases. Although much effort has been made over the years, the precise mechanism of AD has not been completely elucidated. Recently, great attention has shifted to the roles of iron metabolism, lipid peroxidation, and oxidative stress in AD pathogenesis. We also note that these pathological events are the vital regulators of a novel regulatory cell death, termed ferroptosis-an iron-dependent, oxidative, non-apoptotic cell death. Ferroptosis differs from apoptosis, necrosis, and autophagy with respect to morphology, biochemistry, and genetics. Mounting evidence suggests that ferroptosis may be involved in neurological disorders, including AD. Here, we review the underlying mechanisms of ferroptosis; discuss the potential interaction between AD and ferroptosis in terms of iron metabolism, lipid peroxidation, and the glutathione/glutathione peroxidase 4 axis; and describe some associated studies that have explored the implication of ferroptosis in AD.
阿尔茨海默病（AD）是痴呆最常见的病因，约占所有病例的60%-80%。尽管多年来人们付出了诸多努力，但AD的确切机制尚未完全阐明。最近，人们的极大关注已转向铁代谢、脂质过氧化和氧化应激在AD发病机制中的作用。我们还注意到，这些病理事件是一种新型调节性细胞死亡（称为铁死亡——一种铁依赖性、氧化性、非凋亡性细胞死亡）的重要调节因子。铁死亡在形态学、生物化学和遗传学方面不同于凋亡、坏死和自噬。越来越多的证据表明，铁死亡可能参与包括AD在内的神经系统疾病。在此，我们综述铁死亡的潜在机制；从铁代谢、脂质过氧化以及谷胱甘肽/谷胱甘肽过氧化物酶4轴方面讨论AD与铁死亡之间的潜在相互作用；并描述一些探索铁死亡在AD中的意义的相关研究。
