title: Neuromuscular junction degeneration in muscle wasting.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Rüdiger
authors: R
authors: Rudolf
authors: Michael R
authors: MR
authors: Deschenes
authors: Marco
authors: M
authors: Sandri
mesh_terms: D000818:Animals; D001343:Autophagy; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D009124:Muscle Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009133:Muscular Atrophy / Q000209:etiology*; D009410:Nerve Degeneration / Q000209:etiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020511:Neuromuscular Junction Diseases / Q000209:etiology*; D019282:Wasting Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D060449:Wnt Signaling Pathway
chemical_list: D009124:Muscle Proteins; D009419:Nerve Tissue Proteins