Dominant-positive HSF1 decreases alpha-synuclein level and alpha-synuclein-induced toxicity
Dominant-positive HSF1 decreases alpha-synuclein level and alpha-synuclein-induced toxicity
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DOI：
10.1007/s11033-009-9623-2
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发表时间：
2010-04-01
影响因子：
2.8
通讯作者：
Jiangying, Zou
中科院分区：
文献类型：
--
作者：
Liangliang, Xu;Yonghui, Hou;Jiangying, Zou
α-突触核蛋白聚集和细胞毒性被广泛认为在帕金森病的过程中发挥着关键作用。热休克蛋白是大多数细胞中的一大类细胞保护分子。在这项研究中，我们研究了显性阳性热休克转录因子 1 (HSF1) 对帕金森病 α-突触核蛋白过度表达细胞模型的影响。我们发现α-突触核蛋白的过度表达可以形成α-突触核蛋白免疫阳性包涵体并导致细胞死亡；显性阳性HSF1显着增加SH-SY5Y细胞中HSP70的表达，并显着降低α-突触核蛋白的水平和细胞毒性。综上所述，这些数据表明显性阳性 HSF1 在抑制 SH-SY5Y 细胞中的 α-突触核蛋白聚集和毒性方面发挥重要作用。以α-突触核蛋白聚集为特征的帕金森病可以通过增加一组内源性热休克蛋白来治疗。
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.