Rudolf Rüdiger, Deschenes Michael R, Sandri Marco
aInterdisciplinary Center for Neuroscience, University of Heidelberg, Heidelberg bInstitute of Molecular and Cell Biology, Mannheim University of Applied Science, Mannheim cInstitute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany dDepartment of Kinesiology and Health Sciences, The College of William and Mary, Williamsburg, Virginia, USA eDepartment of Biomedical Science, University of Padua fVenetian Institute of Molecular Medicine (VIMM), Padua, Italy.
Curr Opin Clin Nutr Metab Care. 2016 May;19(3):177-81. doi: 10.1097/MCO.0000000000000267.
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-muscle specific kinase-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.
去神经支配是年龄相关性及其他类型肌肉萎缩的一个标志。本综述聚焦于近期有关维持神经肌肉接头以对抗衰老或神经疾病/损伤所致肌肉萎缩的机制及临床相关性的见解和当前观点。
自噬的活动依赖性调节、聚集蛋白-肌肉特异性激酶-Lrp4信号轴以及交感神经调节是稳定神经肌肉接头的主要机制。这些发现源自多种动物模型，并在很大程度上通过人类基因表达分析以及诸如肌萎缩侧索硬化症和先天性肌无力综合征等罕见神经肌肉疾病的研究结果得到证实。基于这些见解，目前正在评估聚集蛋白衍生片段作为年龄相关性肌肉萎缩的生物标志物。对自噬、聚集蛋白途径和交感神经输入的调节正在作为肌肉萎缩性疾病的临床治疗方法进行研究。
基础研究表明，在年龄依赖性及其他形式的肌肉萎缩情况下，维持神经肌肉接头及一些信号通路很重要。这些发现最近已开始进入临床实践，但还需要进一步研究来充实和完善我们的知识。
