BACKGROUND Emerging evidence indicates that inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Several proteins including α-synuclein trigger the activation of NLRP3 inflammasome. However, few studies examined whether inflammasomes are activated in the periphery of PD patients and their possible value in the diagnosis or tracking of the progress of PD. The aim of this study was to determine the association between inflammasome-induced inflammation and clinical features in PD. METHODS There were a total of 67 participants, including 43 patients with PD and 24 controls, in the study. Participants received a complete evaluation of motor and non-motor symptoms, including Hoehn and Yahr (H-Y) staging scale. Blood samples were collected from all participants. The protein and mRNA expression levels of inflammasomes subtypes and components in peripheral blood mononuclear cells (PBMCs) were determined using western blotting and RT-qPCR. We applied Meso Scale Discovery (MSD) immunoassay to measure the plasma levels of IL-1β and α-synuclein. RESULTS We observed increased gene expression of NLRP3, ASC, and caspase-1 in PBMCs, and increased protein levels of NLRP3, caspase-1, and IL-1β in PD patients. Plasma levels of IL-1β were significantly higher in patients with PD compared with controls and have a positive correlation with H-Y stage and UPDRS part III scores. Furthermore, plasma α-synuclein levels were also increased in PD patients and have a positive correlation with both UPDRS part III scores and plasma IL-1β levels. CONCLUSIONS Our data demonstrated that the NLRP3 inflammasome is activated in the PBMCs from PD patients. The related inflammatory cytokine IL-1β and total α-synuclein in plasma were increased in PD patients than controls, and both of them presented a positive correlation with motor severity in patients with PD. Furthermore, plasma α-synuclein levels have a positive correlation with IL-1β levels in PD patients. All these findings suggested that the NLRP3 inflammasome activation-related cytokine IL-1β and α-synuclein could serve as non-invasive biomarkers to monitor the severity and progression of PD in regard to motor function.

中文翻译：

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NLRP3炎性小体和血浆α-突触核蛋白水平的全身激活与帕金森氏病的运动严重性和进展相关。

背景技术越来越多的证据表明，炎性体诱导的炎症在帕金森氏病（PD）的发病机理中起着至关重要的作用。包括α-突触核蛋白在内的几种蛋白质触发NLRP3炎性小体的激活。然而，很少有研究检查炎性小体是否在PD患者的外周被激活，以及它们在PD诊断或追踪PD进展中的可能价值。这项研究的目的是确定炎症小体引起的炎症与PD的临床特征之间的关系。方法共有67名参与者，包括43名PD患者和24名对照。参与者对运动和非运动症状进行了全面评估，包括Hoehn和Yahr（HY）分期量表。从所有参与者收集血液样本。使用western blotting和RT-qPCR检测外周血单个核细胞（PBMC）中炎性小体亚型和组分的蛋白质和mRNA表达水平。我们应用介观规模发现（MSD）免疫测定来测量IL-1β和α-突触核蛋白的血浆水平。结果我们观察到PBMC中NLRP3，ASC和caspase-1的基因表达增加，并且PD患者中NLRP3，caspase-1和IL-1β的蛋白质水平增加。与对照组相比，PD患者的血浆IL-1β水平显着升高，并且与HY分期和UPDRS III部分评分呈正相关。此外，PD患者的血浆α-突触核蛋白水平也升高，并且与UPDRS III部分评分和血浆IL-1β水平呈正相关。结论我们的数据表明NLRP3炎性小体在PD患者的PBMC中被激活。PD患者血浆中相关的炎症细胞因子IL-1β和总α-突触核蛋白水平高于对照组，且两者均与PD患者的运动严重程度呈正相关。此外，PD患者的血浆α-突触核蛋白水平与IL-1β水平呈正相关。所有这些发现表明，NLRP3炎性体激活相关的细胞因子IL-1β和α-突触核蛋白可以作为非侵入性生物标记物，以监测PD在运动功能方面的严重性和进展。他们都与PD患者的运动严重程度呈正相关。此外，在PD患者中血浆α-突触核蛋白水平与IL-1β水平呈正相关。所有这些发现表明，NLRP3炎性体激活相关的细胞因子IL-1β和α-突触核蛋白可以作为非侵入性生物标记物，以监测PD在运动功能方面的严重性和进展。他们都与PD患者的运动严重程度呈正相关。此外，PD患者的血浆α-突触核蛋白水平与IL-1β水平呈正相关。所有这些发现表明，NLRP3炎性体激活相关的细胞因子IL-1β和α-突触核蛋白可以作为非侵入性生物标记物，以监测PD在运动功能方面的严重性和进展。