title: Dimebon does not ameliorate pathological changes caused by expression of truncated (1-120) human alpha-synuclein in dopaminergic neurons of transgenic mice.
abstract: BACKGROUND
  Recent clinical studies have demonstrated that dimebon, a drug originally designed and used as a non-selective antihistamine, ameliorates symptoms and delays progress of mild to moderate forms of Alzheimer's and Huntington's diseases. Although the mechanism of dimebon action on pathological processes in degenerating brain is elusive, results of studies carried out in cell cultures and animal models suggested that this drug might affect the process of pathological accumulation and aggregation of various proteins involved in the pathogenesis of proteinopathies. However, the effect of this drug on the pathology caused by overexpression and aggregation of alpha-synuclein, including Parkinson's disease (PD), has not been assessed.
  
  
  OBJECTIVE
  To test if dimebon affected alpha-synuclein-induced pathology using a transgenic animal model.
  
  
  METHODS
  We studied the effects of chronic dimebon treatment on transgenic mice expressing the C-terminally truncated (1-120) form of human alpha-synuclein in dopaminergic neurons, a mouse model that recapitulates several biochemical, histopathological and behavioral characteristics of the early stage of PD.
  
  
  RESULTS
  Dimebon did not improve balance and coordination of aging transgenic animals or increase the level of striatal dopamine, nor did it prevent accumulation of alpha-synuclein in cell bodies of dopaminergic neurons.
  
  
  CONCLUSIONS
  Our observations suggest that in the studied model of alpha-synucleinopathy dimebon has very limited effect on certain pathological alterations typical of PD and related diseases.
authors.affiliation: Institute of Physiologically Active Compounds RAS, Chernogolovka, Russian Federation, Cambridge, UK.
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Shelkovnikova
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Ustyugov
authors.forename: Steven
authors.initials: S
authors.lastname: Millership
authors.forename: Owen
authors.initials: O
authors.lastname: Peters
authors.forename: Oleg
authors.initials: O
authors.lastname: Anichtchik
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Buchman
authors.forename: Sergey O
authors.initials: SO
authors.lastname: Bachurin
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Ninkina
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004298:Dopamine / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006632:Histamine / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D004856:Postural Balance / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D017557:Ventral Tegmental Area / Q000473:pathology; D051844:alpha-Synuclein / Q000235:genetics* / Q000502:physiology
chemical_list: D015415:Biomarkers; D007211:Indoles; D051844:alpha-Synuclein; D012313:RNA; D006632:Histamine; C010119:latrepirdine; D004298:Dopamine