基于酶活力蛋白质组学技术的谷胱甘肽S转移酶活性探针对帕金森病的研究

帕金森病是一种常见的神经退行性疾病，但目前缺乏早期诊断的可靠特异性指标，只能依靠晚期临床症状作出诊断，并且鉴别诊断困难，因此急需早期诊断的标记分子。本项目的前期工作和其他人对帕金森病已有的研究结果中得到的提示表明，GSTs是帕金森病中对抗氧化应激的重要蛋白酶家族。然而GSTs在帕金森病中的酶活力变化却未见报道。酶活力蛋白质组学技术能够通过活性位点探针，从复杂的蛋白质样本中直接检测出某一类蛋白酶家族的全部成员的酶活力变化。因此本研究拟首次合成GSTs活性位点探针检测帕金森病患者血样中的GSTs酶活力变化，以期找到潜在的帕金森病的早期诊断标记分子，并使用帕金森病细胞模型进一步揭示其在帕金森病中的发病机制。

Parkinson's disease (PD) is a common neurodegenerative disease, but to date, clinical assessment remains the golden standard in the diagnosis of PD. Unfortunatly,it is estimated that when patients develop the symptoms, 70-80% of the dopaminergic neurons have already died. Beside, since several diseases also have similar symptoms with PD，10% or more patients could be misdiagnosed. Therefore, there is a great need for the biomarkers of PD for accurate and early diagnosis. This project will use a recently developed method,the activity-based proteomics to synthesize the first active-site directed probe of glutathione S-transferases (GSTs) by utilizing of derivatives of the GSTs irrversible inhibitor, 7-Nitro-2,1,3-benzoxadiazole which can be covalently binded to the active-site of GSTs, and then use the probe to visualize for the first time, the dynamics of the expression and function of the entire GST family in the blood of the patients with PD. We will also use PD cell model to further investigate how those changes of GSTs are involved in the pathogenisis mechanism of PD. The dynamic changes of the GSTs family gathered by the probe may provide potential early diagnostic and therpeutic targets of PD and will shed light on the mechanism of the dopaminergic neurons' death in PD.