Systemic activation of NLRP3 inflammasome and plasma α-synuclein levels are correlated with motor severity and progression in Parkinson's disease
Systemic activation of NLRP3 inflammasome and plasma α-synuclein levels are correlated with motor severity and progression in Parkinson's disease
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DOI：
10.1186/s12974-019-1670-6
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发表时间：
2020-01-08
影响因子：
9.3
通讯作者：
Wang, Xiao-Min
中科院分区：
文献类型：
--
作者：
Fan, Zheng;Pan, Yu-Ting;Wang, Xiao-Min
研究背景近年来，越来越多的证据表明，炎症小体诱导的炎症反应在帕金森病（PD）的发病机制中起着至关重要的作用。包括α-突触核蛋白的几种蛋白质触发NLRP 3炎性体的激活。然而，很少有研究检查炎症小体是否在PD患者的外周被激活，以及它们在诊断或跟踪PD进展中的可能价值。本研究的目的是确定炎性小体诱导的炎症与PD临床特征之间的相关性。方法67例PD患者和24例正常对照者参加研究。参与者接受了完整的运动和非运动症状评估，包括Hoehn和Yahr（H-Y）分期量表。从所有参与者中采集血液样本。采用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和mRNA表达水平。我们应用Meso Scale Discovery（MSD）免疫测定法测定IL-1 β和α-突触核蛋白的血浆水平。结果我们观察到PD患者PBMC中NLRP 3、ASC和caspase-1的基因表达增加，NLRP 3、caspase-1和IL-1 β的蛋白水平增加。与对照组相比，PD患者的血浆IL-1 β水平显著升高，并与H-Y分期和APPLICATRS第III部分评分呈正相关。此外，PD患者的血浆α-突触核蛋白水平也增加，并与PDRS第III部分评分和血浆IL-1 β水平呈正相关。结论NLRP 3炎性小体在PD患者PBMC中存在活化。PD患者血浆中相关炎症细胞因子IL-1 β和总α-突触核蛋白水平均高于对照组，且均与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-1 β水平呈正相关。所有这些发现表明，NLRP 3炎性体激活相关的细胞因子IL-1 β和α-突触核蛋白可以作为非侵入性生物标志物来监测运动功能方面的PD的严重程度和进展。
Background Emerging evidence indicates that inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Several proteins including alpha-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-1 beta and alpha-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-1 beta in PD patients. Plasma levels of IL-1 beta 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 alpha-synuclein levels were also increased in PD patients and have a positive correlation with both UPDRS part III scores and plasma IL-1 beta levels. Conclusions Our data demonstrated that the NLRP3 inflammasome is activated in the PBMCs from PD patients. The related inflammatory cytokine IL-1 beta and total alpha-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 alpha-synuclein levels have a positive correlation with IL-1 beta levels in PD patients. All these findings suggested that the NLRP3 inflammasome activation-related cytokine IL-1 beta and alpha-synuclein could serve as non-invasive biomarkers to monitor the severity and progression of PD in regard to motor function.