title: The HSP70 molecular chaperone is not beneficial in a mouse model of alpha-synucleinopathy.
abstract: BACKGROUND
  Aggregation and misfolded alpha-synuclein is thought to be central in the pathogenesis of Parkinson's disease (PD). Heat-shock proteins (HSPs) that are involved in refolding and degradation processes could lower the aggregate load of alpha-synuclein and thus be beneficial in alpha-synucleinopathies.
  
  
  RESULTS
  We co-overexpressed human A53T point-mutated alpha-synuclein and human HSP70 in mice, both under the control of Thy1 regulatory sequences. Behavior read-outs showed no beneficial effect of HSP70 expression in mice. In contrast, motor coordination, grip strength and weight were even worse in the alpha-synucleinopathy model in the presence of HSP70 overexpression. Biochemical analyses revealed no differences in alpha-synuclein oligomers/aggregates, truncations and phosphorylation levels and alpha-synuclein localization was unchanged in immunostainings.
  
  
  CONCLUSIONS
  Overexpressing HSP70 in a mouse model of alpha-synucleinopathy did not lower the toxic load of alpha-synuclein species and had no beneficial effect on alpha-synuclein-related motor deficits.
authors.affiliation: Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland. derya.shimshek@novartis.com
authors.forename: Derya R
authors.initials: DR
authors.lastname: Shimshek
authors.forename: Matthias
authors.initials: M
authors.lastname: Mueller
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiessner
authors.forename: Tatjana
authors.initials: T
authors.lastname: Schweizer
authors.forename: P Herman
authors.initials: PH
authors.lastname: van der Putten
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D015316:Genetic Therapy; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D018737:Hand Strength; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D017354:Point Mutation; D017510:Protein Folding; D055503:Protein Multimerization; D017211:Treatment Failure; D051844:alpha-Synuclein / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics
chemical_list: D018840:HSP70 Heat-Shock Proteins; D051844:alpha-Synuclein