Table_1_Abnormal Vacuole Membrane Protein-1 Expression in Parkinson’s Disease Patients.DOCX

BackgroundParkinson’s disease (PD) is pathologically characterized by progressive dopaminergic (DAergic) neuron loss in the substantia nigra pars compacta (SNpc) and accumulation of intracytoplasmic α-synuclein-containing Lewy bodies. Autophagy has been identified as a critical component in the development and progression of PD. Several autophagy genes have been identified as being altered in PD. One of those genes, vacuole membrane protein-1 (VMP1), an autophagy protein localized in the endoplasmic reticulum (ER) in DAergic neurons, has been shown to cause motor disorder, severe loss of DAergic neurons, and autophagy flux disturbance in the VMP1 knockout mouse model.
ObjectiveTo evaluate for the first time the alteration on the expression of the VMP1 gene and its clinical correlations in peripheral blood mononuclear cells (PBMCs) of a relatively large sample of PD patients.
MethodsWe assessed the VMP1 mRNA levels in PD patients (n = 229) and healthy controls (HC) (n = 209) using real-time quantitative PCR (RT-qPCR), and the VMP1 protein levels in PD patients (n = 27) and HC (n = 27) using Western blot (WB). Then, we analyzed the VMP1 expression levels and clinical features of PD patients.
ResultsOur findings revealed that VMP1 levels in the PD group were significantly lower than in the HC group (RT-qPCR p < 0.01 and WB p < 0.001). The VMP1 expression was significantly lower as the disease progressed, which could be ameliorated by administering DAergic receptor agonists. Moreover, receiver operating characteristic (ROC) curve analysis showed that VMP1 mRNA and protein level area under the curves (AUCs) were 64.5%, p < 0.01, and 83.4%, p < 0.01, respectively.
ConclusionThis case-control study demonstrates that peripheral VMP1 level altered in PD patients and may serve as a potential endogenous diagnostic marker of PD.

**研究背景** 帕金森病（Parkinson’s disease, PD）的病理特征为黑质致密部（substantia nigra pars compacta, SNpc）进行性多巴胺能（dopaminergic, DAergic）神经元丢失，以及胞浆内含α-突触核蛋白的路易小体聚集。自噬（autophagy）在帕金森病的发生发展中发挥关键作用，多项自噬相关基因在帕金森病中被发现存在异常。其中，空泡膜蛋白-1（vacuole membrane protein-1, VMP1）是定位于多巴胺能神经元内质网（endoplasmic reticulum, ER）的自噬相关蛋白，在VMP1基因敲除小鼠模型中，该蛋白缺失可引发运动障碍、多巴胺能神经元严重丢失以及自噬流紊乱。
**研究目的** 首次探讨帕金森病患者大样本外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）中VMP1基因的表达变化及其临床相关性。
**研究方法** 本研究采用实时定量聚合酶链反应（real-time quantitative PCR, RT-qPCR）检测229例帕金森病患者与209例健康对照者（healthy controls, HC）外周血中VMP1的mRNA水平；同时采用蛋白质印迹（Western blot, WB）检测27例帕金森病患者与27例健康对照者外周血中VMP1的蛋白水平。随后分析帕金森病患者VMP1的表达水平与临床特征的关联。
**研究结果** 结果显示，帕金森病患者组的VMP1表达水平显著低于健康对照组（RT-qPCR检测结果：p<0.01；WB检测结果：p<0.001）。随着疾病进展，VMP1的表达水平进一步降低，而多巴胺能受体激动剂治疗可改善这一现象。此外，受试者工作特征（receiver operating characteristic, ROC）曲线分析显示，VMP1 mRNA与蛋白水平的曲线下面积（area under the curves, AUCs）分别为64.5%（p<0.01）与83.4%（p<0.01）。
**研究结论** 本病例对照研究表明，帕金森病患者外周血VMP1水平存在异常，有望成为帕金森病潜在的内源性诊断标志物。