Role and Mechanisms of Action of Anabolic Stimuli on Neuromuscular Trophicity

点击翻译按钮获取中文摘要

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.