title: Lovastatin corrects ERK pathway hyperactivation in fragile X syndrome: potential of platelet's signaling cascades as new outcome measures in clinical trials.
abstract: OBJECTIVE
  To establish whether platelets from fragile X syndrome (FXS) individuals recapitulate FXS mouse neurons' defects in ERK and Akt pathways, and to evaluate the effect of lovastatin on these pathways.
  
  
  METHODS
  ERK and Akt phosphorylation (pERK, pAkt) statuses were assessed with quantitative Western blotting before and after a 12-week lovastatin trial.
  
  
  RESULTS
  Levels of pERK and pAkt were increased in FXS platelets, and lovastatin specifically normalized ERK activity. Changes in ERK phosphorylation were correlated with clinical response to lovastatin.
  
  
  CONCLUSIONS
  Platelets' signaling pathways provide biomarkers that can be used as treatment outcome measures in FXS clinical trials.
authors.affiliation: a Department of Biochemistry, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , QC , Canada.
authors.forename: David
authors.initials: D
authors.lastname: Pellerin
authors.affiliation: a Department of Biochemistry, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , QC , Canada.
authors.forename: Artuela
authors.initials: A
authors.lastname: Çaku
authors.affiliation: a Department of Biochemistry, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , QC , Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Fradet
authors.affiliation: a Department of Biochemistry, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , QC , Canada.
authors.forename: Paméla
authors.initials: P
authors.lastname: Bouvier
authors.affiliation: a Department of Biochemistry, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , QC , Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Dubé
authors.affiliation: a Department of Biochemistry, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , QC , Canada.
authors.forename: François
authors.initials: F
authors.lastname: Corbin
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002986:Clinical Trials as Topic; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005600:Fragile X Syndrome / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D008148:Lovastatin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Akt; biomarkers; blood platelets; genetic diseases; study model