Dominant-positive HSF1 decreases alpha-synuclein level and alpha-synuclein-induced toxicity.
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.
Liangliang
Xu
X
School of Life Sciences, University of Science and Technology of China, 230027, Hefei, China.
Yonghui
Hou
H
Shunmei
E
E
Shoufang
Gong
G
Wei
Zhou
Z
Jiangying
Zou
Z
D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005799:Genes, Dominant; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D020836:Protein Structure, Quaternary; D014157:Transcription Factors / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D051844:alpha-Synuclein