机构：[D]epartment of Pharmacology, School of Basic Medical Sciences, CapitalMedical University, Beijing, China[2]Department of Neurology, XuanwuHospital of Capital Medical University, No[45]Changchun Street, Beijing100053, China[3]Department of Neurobiology, School of Basic MedicalSciences, Capital Medical University, No[10]Xitoutiao, Youanmenwai, Beijing100069, China[4]Department of Physiology, School of Basic Medical Sciences,Capital Medical University, Beijing, China[5]Core Facility Center, CapitalMedical University, Beijing, China[6]Preventive Medicine, School of PublicHealth, Capital Medical University, Beijing, China
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.
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.
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.
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.
基金：
Basic Clinical Collaboration Foundation of
Capital Medical University (no. 17JL26) and the Scientific Research Common
Program of Beijing Municipal Commission of Education (no.
KM201810025001).
通讯机构：[2]Department of Neurology, XuanwuHospital of Capital Medical University, No[3]Department of Neurobiology, School of Basic MedicalSciences, Capital Medical University, No
推荐引用方式(GB/T 7714)：
Zheng Fan,Yu-Ting Pan,Zhi-Yuan Zhang,et al.Systemic activation of NLRP3 inflammasome and plasma α-synuclein levels are correlated with motor severity and progression in Parkinson's disease.[J].JOURNAL OF NEUROINFLAMMATION.2020,17(1):11.doi:10.1186/s12974-019-1670-6.
APA：
Zheng Fan,Yu-Ting Pan,Zhi-Yuan Zhang,Hui Yang,Shu-Yue Yu...&Xiao-Min Wang.(2020).Systemic activation of NLRP3 inflammasome and plasma α-synuclein levels are correlated with motor severity and progression in Parkinson's disease..JOURNAL OF NEUROINFLAMMATION,17,(1)
MLA：
Zheng Fan,et al."Systemic activation of NLRP3 inflammasome and plasma α-synuclein levels are correlated with motor severity and progression in Parkinson's disease.".JOURNAL OF NEUROINFLAMMATION 17..1(2020):11
医学