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铁死亡的机制及其与神经退行性疾病病理学的新联系

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases.

作者信息

Sun Yiyan, Xia Xiaohuan, Basnet Diksha, Zheng Jialin C, Huang Jian, Liu Jianhui

机构信息

Department of Anesthesiology, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

出版信息

Front Aging Neurosci. 2022 Jun 28;14:904152. doi: 10.3389/fnagi.2022.904152. eCollection 2022.

Abstract

Neurodegenerative diseases are a diverse class of diseases attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. The pathogenesis of neurodegenerative diseases is complex and diverse, often involving mitochondrial dysfunction, neuroinflammation, and epigenetic changes. However, the pathogenesis of neurodegenerative diseases has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, a newly discovered iron-dependent and lipid peroxidation-driven type of programmed cell death, provides another explanation for the occurrence and progression of neurodegenerative diseases. Here, we provide an overview of the process and regulation mechanisms of ferroptosis, and summarize current research progresses that support the contribution of ferroptosis to the pathogenesis of neurodegenerative diseases. A comprehensive understanding of the emerging roles of ferroptosis in neurodegenerative diseases will shed light on the development of novel therapeutic technologies and strategies for slowing down the progression of these diseases.

摘要

神经退行性疾病是一类多样的疾病,归因于大脑和/或脊髓中慢性进行性神经元变性和突触丧失,包括阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和多发性硬化症。神经退行性疾病的发病机制复杂多样,常涉及线粒体功能障碍、神经炎症和表观遗传变化。然而,神经退行性疾病的发病机制尚未完全阐明。最近,越来越多的证据表明,铁死亡是一种新发现的由铁依赖性和脂质过氧化驱动的程序性细胞死亡类型,为神经退行性疾病的发生和发展提供了另一种解释。在此,我们概述了铁死亡的过程和调控机制,并总结了支持铁死亡在神经退行性疾病发病机制中作用的当前研究进展。全面了解铁死亡在神经退行性疾病中的新作用将为开发减缓这些疾病进展的新型治疗技术和策略提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1397/9273851/b198d80017a3/fnagi-14-904152-g001.jpg

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