| First Author | Shimshek DR | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 4 | Pages | e10014 |
| PubMed ID | 20368804 | Mgi Jnum | J:160180 |
| Mgi Id | MGI:4453538 | Doi | 10.1371/journal.pone.0010014 |
| Citation | Shimshek DR, et al. (2010) The HSP70 molecular chaperone is not beneficial in a mouse model of alpha-synucleinopathy. PLoS One 5(4):e10014 |
| abstractText | 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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. |
