| α-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. Recent studies have demenstrated some heat shock proteins could inhibitα-synuclein aggregation and toxicity. In eukaryotic cells, HSF1 (heat shock transcription factor 1) is the main specific transcription factors mediating the enhanced expression of HSPs when cells experience stresses. It is kept in a latent state by inhibitory complexes including HSP90 under unstressed conditions. HSF1 is only transiently activated in response to diverse forms of physiological and environmental stresses. Domiantly positive HSF1 has been developed through point-mutation or deletion-mutation. In this study, we examined the impact of dominant-positive HSF1(HSF1(+)) onα-synuclein over-expression cellular model of Parkinson's disease. We found that over-expression ofα-synuclein could formα-synuclein immunopositive inclusions and result in cell death; HSF1(+) dramatically increased the expression of HSP70 in SH-SY5Y cells, the level of HSP27 and HSP90 was also slightly increased; Co-expression of HSF1(+) significantly decreased the level and cytotoxicity ofα-synuclein, and the cells containingα-synuclein immunopositive inclusions were also decreased. In addition, the apotosis induced by 6-OHDA was significantly inhibited by HSF1(+). Taken together, these data indicate that dominant-positive HSF1 not only plays an important role in suppressingα-synuclein aggregation and toxicity, but also in inhibiting 6-OHDA toxicity in SH-SY5Y cells. Parkinson's disease which is marked byα-synuclein aggregation may be treated by increasing a set of endogenous heat shock proteins.
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