Neuromuscular junction degeneration in muscle wasting.
Neuromuscular junction degeneration in muscle wasting.
复制标题
肌肉浪费中的神经肌肉连接变性。
DOI：
10.1097/mco.0000000000000267
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发表时间：
2016-05
影响因子：
3.1
通讯作者：
Sandri M
中科院分区：
文献类型：
--
作者：
Rudolf R;Deschenes MR;Sandri M
失神经是与年龄相关的和其他类型的肌肉萎缩的一个标志。本文就维持神经肌肉连接以对抗因衰老或神经疾病/损伤引起的肌肉萎缩的机制和临床相关性的最新见解和最新观点进行综述。依赖活动的自噬调节、agrin-Musk-Lrp4信号轴和交感调制是稳定神经肌肉接头的主要机制。这些发现来自几个动物模型，并在很大程度上被人类基因表达分析以及对罕见的神经肌肉疾病(如肌萎缩侧索硬化症和先天性肌无力综合征)的洞察所证实。基于这些见解，集聚蛋白衍生的片段目前被评估为与年龄相关的肌肉萎缩的生物标记物。自噬、集聚蛋白途径和交感神经输入的调节作为肌肉萎缩障碍的临床治疗正在被研究。基础研究表明，在年龄依赖性和其他形式的肌肉萎缩的背景下，维持神经肌肉连接和一些信号通路是重要的。这些发现最近开始进入临床实践，但需要进一步的研究来证实和完善我们的知识。
Denervation is a hallmark of age-related and other types of muscle wasting. This review focuses on recent insights and current viewpoints regarding the mechanisms and clinical relevance of maintaining the neuromuscular junction to counteract muscle wasting resulting from aging or neural disease/damage. Activity-dependent regulation of autophagy, the agrin-MuSK-Lrp4 signaling axis, and sympathetic modulation are principal mechanisms involved in stabilizing the neuromuscular junction. These findings are derived from several animal models and were largely confirmed by human gene expression analysis as well as insights from rare neuromuscular diseases such as amyotrophic lateral sclerosis and congenital myasthenic syndromes. Based on these insights, agrin-derived fragments are currently being evaluated as biomarkers for age-related muscle wasting. Tuning of autophagy, of the agrin pathway, and of sympathetic input are being studied as clinical treatment of muscle wasting disorders. Basic research has revealed that maintenance of neuromuscular junctions and a few signaling pathways are important in the context of age-dependent and other forms of muscle wasting. These findings have recently started to enter clinical practice, but further research needs to substantiate and refine our knowledge.