肌萎缩性侧索硬化症中线粒体功能障碍驱动神经肌肉连接处变性的分子机制。

IF 5.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2025-09-15 DOI:10.1016/j.nbd.2025.107103

Xie Yipeng , Wang Guiqian , Zhu Qiaochu , He Tengjie , Zhao Yan , Huang Hai , Zhou Jing

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引用次数: 0

摘要

背景：肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是运动神经元进行性变性和神经肌肉连接（NMJs）的早期退化。越来越多的证据表明，线粒体功能障碍在ALS患者NMJ变性中起关键作用。目的：本文旨在全面总结线粒体缺陷导致NMJ不稳定的分子机制，特别关注生物能量学、钙稳态、氧化应激和线粒体生物发生受损。结论：线粒体功能障碍是ALS患者NMJ变性的核心驱动因素。靶向线粒体生物发生和代谢-特别是通过PGC-1α途径-代表了一种有希望的策略，以保持NMJ完整性和减缓疾病进展。

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Molecular mechanisms by which mitochondrial dysfunction drives neuromuscular junction degeneration in amyotrophic lateral sclerosis

Background

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive degeneration of motor neurons and early deterioration of neuromuscular junctions (NMJs). Increasing evidence indicates that mitochondrial dysfunction plays a pivotal role in driving NMJ degeneration in ALS.

Objective

This review aims to comprehensively summarize the molecular mechanisms by which mitochondrial defects contribute to NMJ instability, with a particular focus on bioenergetics, calcium homeostasis, oxidative stress, and impaired mitochondrial biogenesis.

Conclusion

Mitochondrial dysfunction is a core driver of NMJ degeneration in ALS. Targeting mitochondrial biogenesis and metabolism—particularly through the PGC-1α pathway—represents a promising strategy to preserve NMJ integrity and slow disease progression.

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.