Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, 250062 Jinan, Shandong, China.
Public Health Monitoring and Evaluation Institute of Shandong Provincial Center for Disease Control and Prevention, 250000 Jinan, Shandong, China.
Front Biosci (Landmark Ed). 2024 Aug 20;29(8):291. doi: 10.31083/j.fbl2908291.
Neurodegenerative disorders are typified by the progressive degeneration and subsequent apoptosis of neuronal cells. They encompass a spectrum of conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), epilepsy, brian ischemia, brian injury, and neurodegeneration with brain iron accumulation (NBIA). Despite the considerable heterogeneity in their clinical presentation, pathophysiological underpinning and disease trajectory, a universal feature of these disorders is the functional deterioration of the nervous system concomitant with neuronal apoptosis. Ferroptosis is an iron (Fe)-dependent form of programmed cell death that has been implicated in the pathogenesis of these conditions. It is intricately associated with intracellular Fe metabolism and lipid homeostasis. The accumulation of Fe is observed in a variety of neurodegenerative diseases and has been linked to their etiology and progression, although its precise role in these pathologies has yet to be elucidated. This review aims to elucidate the characteristics and regulatory mechanisms of ferroptosis, its association with neurodegenerative diseases, and recent advances in ferroptosis-targeted therapeutic strategies. Ferroptosis may therefore be a critical area for future research into neurodegenerative diseases.
神经退行性疾病的特点是神经元细胞的进行性退化和随后的细胞凋亡。它们包括一系列病症,包括阿尔茨海默病(AD)、帕金森病(PD)、肌萎缩侧索硬化症(ALS)、亨廷顿病(HD)、癫痫、脑缺血、脑损伤和脑铁积累相关的神经退行性疾病(NBIA)。尽管它们在临床表现、病理生理学基础和疾病进程方面存在很大的异质性,但这些疾病的一个普遍特征是神经系统的功能恶化伴随着神经元凋亡。铁死亡是一种铁(Fe)依赖性的程序性细胞死亡形式,已被认为与这些疾病的发病机制有关。它与细胞内 Fe 代谢和脂质稳态密切相关。在各种神经退行性疾病中观察到 Fe 的积累,并与它们的病因和进展有关,尽管其在这些病理中的确切作用尚未阐明。本综述旨在阐明铁死亡的特征和调节机制,及其与神经退行性疾病的关联,以及铁死亡靶向治疗策略的最新进展。因此,铁死亡可能是神经退行性疾病未来研究的一个关键领域。
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