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铁死亡在肌萎缩侧索硬化症治疗中的作用。

The Role of Ferroptosis in Amyotrophic Lateral Sclerosis Treatment.

机构信息

Yan 'an Small Molecule Innovative Drug R&D Engineering Research Center, School of Medicine, Yan'an University, Yan'an, China.

College of Physical Education, Yan'an University, Shaanxi, 716000, China.

出版信息

Neurochem Res. 2024 Oct;49(10):2653-2667. doi: 10.1007/s11064-024-04194-w. Epub 2024 Jun 12.

Abstract

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.

摘要

肌萎缩侧索硬化症(ALS)是一种罕见的神经退行性疾病,由于其复杂的发病机制和有限的临床药物,治疗极具挑战性。铁死亡是一种依赖铁的程序性细胞死亡(PCD)形式,与细胞凋亡、坏死、自噬和其他细胞死亡机制明显不同。最近的研究越来越多地强调铁沉积、活性氧(ROS)积累、氧化应激以及抗氧化系统中系统 Xc 和谷氨酸积累在肌萎缩侧索硬化症发病机制中的作用。因此,靶向铁死亡成为肌萎缩侧索硬化症治疗的一种有前途的策略。本综述介绍了铁死亡的调控机制、肌萎缩侧索硬化症与铁死亡的关系以及临床应用的药物,然后讨论了肌萎缩侧索硬化症的治疗现状,希望为其治疗提供新的方向和靶点。

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