Wu Linyu, Xian Xiaohui, Tan Zixuan, Dong Fang, Xu Guangyu, Zhang Min, Zhang Feng
Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, 050051, Hebei, People's Republic of China.
Department of Pathophysiology, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, 050051, Hebei, People's Republic of China.
Mol Neurobiol. 2023 May;60(5):2832-2850. doi: 10.1007/s12035-023-03245-7. Epub 2023 Feb 3.
In the development of Alzheimer's disease (AD), cell death is common. Novel cell death form-ferroptosis is discovered in recent years. Ferroptosis is an iron-regulated programmed cell death mechanism and has been identified in AD clinical samples. Typical characteristics of ferroptosis involve the specific changes in cell morphology, iron-dependent aggregation of reactive oxygen species (ROS) and lipid peroxides, loss of glutathione (GSH), inactivation of glutathione peroxidase 4 (GPX4), and a unique group of regulatory genes. Increasing evidence demonstrates that ferroptosis may be associated with neurological dysfunction in AD. However, the underlying mechanisms have not been fully elucidated. This article reviews the potential role of ferroptosis in AD, the involvement of ferroptosis in the pathological progression of AD through the mechanisms of iron metabolism, lipid metabolism, and redox homeostasis, as well as a range of potential therapies targeting ferroptosis for AD. Intervention strategies based on ferroptosis are promising for Alzheimer's disease treatment at present, but further researches are still needed.
在阿尔茨海默病（AD）的发展过程中，细胞死亡很常见。近年来发现了一种新的细胞死亡形式——铁死亡。铁死亡是一种铁调节的程序性细胞死亡机制，已在AD临床样本中得到证实。铁死亡的典型特征包括细胞形态的特定变化、活性氧（ROS）和脂质过氧化物的铁依赖性聚集、谷胱甘肽（GSH）的丧失、谷胱甘肽过氧化物酶4（GPX4）的失活以及一组独特的调控基因。越来越多的证据表明，铁死亡可能与AD中的神经功能障碍有关。然而，其潜在机制尚未完全阐明。本文综述了铁死亡在AD中的潜在作用、铁死亡通过铁代谢、脂质代谢和氧化还原稳态机制参与AD的病理进展，以及一系列针对AD铁死亡的潜在治疗方法。目前，基于铁死亡的干预策略对阿尔茨海默病治疗具有前景，但仍需要进一步研究。
