title: Charcot-Marie-Tooth disease: an update.
abstract: OBJECTIVE
  The purpose of this review is to assist neurologists, neuroscientists and other interested readers in following the expanding volume of information relating to the inherited peripheral neuropathies collectively referred to as Charcot-Marie-Tooth disease. Currently, mutations in multiple different genes expressed in Schwann cells and neurons cause a variety of overlapping clinical phenotypes.
  
  
  RESULTS
  Recent articles clarify molecular pathways involved in the pathogenesis of these disorders, and for the first time provide rational treatment strategies for the most common form of Charcot-Marie-Tooth disease. The identification of many new genes associated with neuropathy demonstrate the role of axonal transport and abnormal protein trafficking in causing various forms of Charcot-Marie-Tooth. They also further define the role of axonal signaling and the molecular architecture of both Schwann cells and neurons in maintaining normal peripheral nervous system function. Finally, recent reports have shown that progesterone antagonists and ascorbic acid can successfully treat rodent models of Charcot-Marie-Tooth disease type 1A.
  
  
  CONCLUSIONS
  Taken together, results from these articles support the concept that genetic causes of Charcot-Marie-Tooth disease serve as a living microarray system to identify molecules necessary for normal peripheral nervous system function. When we can make sense of these microarrays we are likely to understand the pathogenesis and develop rational therapies for many neurodegenerative diseases including Charcot-Marie-Tooth.
authors.affiliation: Department of Neurology, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA. m.shy@wayne.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Shy
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000627:therapeutic use; D001370:Axonal Transport / Q000502:physiology; D002607:Charcot-Marie-Tooth Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D020558:GTP Phosphohydrolases; D006032:Glycine-tRNA Ligase / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000037:antagonists & inhibitors; D021381:Protein Transport / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D006360:Heat-Shock Proteins; C118738:LITAF protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009185:Myelin Proteins; D009687:Nuclear Proteins; C073687:PMP22 protein, human; D014157:Transcription Factors; D000090802:rab7 GTP-Binding Proteins; D011374:Progesterone; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C475072:SBF2 protein, human; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; D020691:rab GTP-Binding Proteins; D006032:Glycine-tRNA Ligase; D001205:Ascorbic Acid