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mTOR在肌萎缩侧索硬化症中的作用。

The Role of mTOR in Amyotrophic Lateral Sclerosis.

作者信息

Nogueira-Machado José Augusto, Rocha-Silva Fabiana, Gomes Nathalia Augusta

机构信息

Stricto Sensu Postgraduate Program in Medicine/Biomedicine, Santa Casa de Belo Horizonte College, Belo Horizonte 30110-005, Brazil.

出版信息

Biomedicines. 2025 Apr 13;13(4):952. doi: 10.3390/biomedicines13040952.

Abstract

Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and incurable disease characterized by muscle weakness and paralysis. Recent studies have explored a possible link between ALS pathophysiology and mTOR signaling. Recent reports have linked the accumulation of protein aggregates, dysfunctional mitochondria, and homeostasis to the development of ALS. mTOR plays a pivotal role in controlling autophagy and affecting energy metabolism, in addition to supporting neuronal growth, plasticity, and the balance between apoptosis and autophagy, all of which are important for homeostasis. This mini-review approaches the regulatory roles of mTOR signaling pathways, their interaction with other metabolic pathways, and their potential to modulate ALS progression. It discusses how these metabolic signaling pathways affect the neuromuscular junction, producing symptoms of muscle weakness and atrophy similar to those seen in patients with ALS. The discussion includes the concepts of neurocentric and peripheral and the possible connection between mTOR and neuromuscular dysfunction in ALS. It highlights the therapeutic potential of mTOR signaling and interconnections with other metabolic routes, making it a promising biomarker and therapeutic target for ALS.

摘要

肌萎缩侧索硬化症(ALS)是一种罕见的、进行性的且无法治愈的疾病,其特征为肌肉无力和瘫痪。最近的研究探讨了ALS病理生理学与mTOR信号传导之间的可能联系。最近的报告将蛋白质聚集体的积累、线粒体功能障碍和体内平衡与ALS的发展联系起来。mTOR除了支持神经元生长、可塑性以及细胞凋亡和自噬之间的平衡(所有这些对体内平衡都很重要)之外,在控制自噬和影响能量代谢方面也起着关键作用。本综述探讨了mTOR信号通路的调节作用、它们与其他代谢途径的相互作用以及它们调节ALS进展的潜力。它讨论了这些代谢信号通路如何影响神经肌肉接头,产生与ALS患者相似的肌肉无力和萎缩症状。讨论内容包括以神经为中心和外周的概念以及mTOR与ALS中神经肌肉功能障碍之间的可能联系。它强调了mTOR信号传导的治疗潜力以及与其他代谢途径的相互联系,使其成为ALS有前景的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf8/12025168/133539a49ef1/biomedicines-13-00952-g001.jpg

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