帕金森病(PD)是一种常见的神经退行性疾病，其发病机制与内质网应激密切相关。硫氧还蛋白-1(Trx-1)是细胞内重要的氧化还原调节蛋白，具有神经保护作用。分子伴侣热休克蛋白90-细胞分裂周期蛋白37(Hsp90-Cdc37)对于维持IRE 1α的稳定性具有关键作用。申请者前期研究发现：在PD模型中，Trx-1通过抑制IRE 1α通路的活化保护多巴胺能神经元免受损伤。然而，Trx-1调节IRE 1α活化的分子机制依然不清楚。本项目拟用PC12细胞和C57BL/6小鼠构建模型，以Hsp90-Cdc37在IRE 1α活化中的作用为切入点，结合高表达、RNA干扰、蛋白质共定位、免疫共沉淀、免疫印记和real-time PCR等生物学手段，研究Trx-1在MPP+/MPTP PD模型中起神经保护作用的分子机制。预期研究成果将对揭示PD的发病机理具有重要的意义，同时为防治PD进一步提供理论依据。

Parkinson’s disease (PD) is a common neurodegenerative disorder, which is closely related to endoplasmic reticulum stress. Thioredoxin-1(Trx-1) is an important endocellular redox protein and plays a neuroprotective role. Chaperones heat shock protein 90-cell division cycle 37(Hsp90-Cdc37) are critrial for the stability of inositol-requiring enzyme 1α(IRE 1α). Our previous studies found that Trx-1 could protect dopaminergic neurons from damage via inhibiting the activation of IRE 1α in PD models. However, the molecular mechanism remains largely unknown. In this project, we will research the mechanism of the protection of Trx-1 in MPP+/MPTP models of PD through studying the action of Hsp90-Cdc37 in the IRE 1α pathway activation in pheochromocytoma PC12 cells and C57BL/6 mice by using the biological methods of overexpression, RNA interference, protein colocalization, co-immunoprecipitation, immunoblotting and real-time PCR. The expected results will be of significance for revealing the pathogenesis of PD and further provide theory evidence for the prevention and treatment of PD.