Dominant-positive HSF1 decreases alpha-synuclein level and alpha-synuclein-induced toxicity

Mol Biol Rep. 2010 Apr;37(4):1875-81. doi: 10.1007/s11033-009-9623-2. Epub 2009 Jul 17.

Abstract

Alpha-synuclein aggregation and cytotoxicity are widely considered to play a critical role in the process of Parkinson's disease. Heat shock proteins are a large family of cellular protective molecules in most kinds of cells. In this study, we examined the impact of dominant-positive heat shock transcription factor 1 (HSF1) on alpha-synuclein over-expression cellular model of Parkinson's disease. We found that over-expression of alpha-synuclein could form alpha-synuclein immunopositive inclusions and result in cell death; dominant-positive HSF1 dramatically increased the expression of HSP70 in SH-SY5Y cells, and significantly decreased the level and cytotoxicity of alpha-synuclein. Taken together, these data indicate that dominant-positive HSF1 plays an important role in suppressing alpha-synuclein aggregation and toxicity in SH-SY5Y cells. Parkinson's disease which is marked by alpha-synuclein aggregation may be treated by increasing a set of endogenous heat shock proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytoprotection / drug effects
  • DNA-Binding Proteins / metabolism*
  • Genes, Dominant*
  • HSP70 Heat-Shock Proteins / genetics
  • Heat Shock Transcription Factors
  • Humans
  • Promoter Regions, Genetic / genetics
  • Protein Structure, Quaternary
  • Transcription Factors / metabolism*
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*
  • alpha-Synuclein / toxicity*

Substances

  • DNA-Binding Proteins
  • HSF1 protein, human
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Transcription Factors
  • alpha-Synuclein