Role and Mechanisms of Action of Anabolic Stimuli on Neuromuscular Trophicity

该项目的第一个资助期揭示了神经肌肉连接（NMJs）是直接交感神经支配的目标。我们发现这种神经支配对NMJs的维持和影响AChR基因表达和囊泡运输的调节具有重要意义。特别是，NMJs的交感神经支配与achr的内溶酶体和自噬加工之间的联系变得明显。在这个项目的扩展中，我们建议：1)使用在第一个资助期创建的新型小鼠品系，对骨骼肌的交感神经支配进行更深入的表征；2)解决交感神经支配状态与人类神经肌肉疾病的系统联系；3)通过蛋白质组学方法确定NMJs交感神经支配的机制靶点。我们希望这项研究能够进一步深入了解骨骼肌交感神经支配的病理生理作用和机制，并揭示神经肌肉疾病的潜在治疗策略。

The first funding period of this project has revealed that neuromuscular junctions (NMJs) are targets of direct sympathetic innervation. We found this innervation to be of eminent importance for the maintenance of NMJs, and to affect the regulation of AChR gene expression and vesicular trafficking. In particular, a link of sympathetic innervation of NMJs to endolysosomal and autophagic processing of AChRs became evident. In the extension of this project we propose to 1). pursue a more in-depth characterization of sympathetic innervation of skeletal muscle using a novel mouse line created during the first funding period, to 2). address a systematic link of sympathetic innervation status to human neuromuscular disease, and to 3). identify the mechanistic targets of sympathetic innervation of NMJs by proteomics approaches. We expect this research to considerably further our insights into the pathophysiological role and mechanisms of sympathetic innervation of skeletal muscle and to reveal potential treatment strategies of neuromuscular diseases.