Adams Büin, Nunes J Massimo, Page Martin J, Roberts Timothy, Carr Jonathan, Nell Theo A, Kell Douglas B, Pretorius Etheresia
Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.
Department of Biochemistry, Institute of Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.
Front Aging Neurosci. 2019 Aug 27;11:210. doi: 10.3389/fnagi.2019.00210. eCollection 2019.
Parkinson's disease (PD) is a well-known neurodegenerative disease with a strong association established with systemic inflammation. Recently, the role of the gingipain protease group from was implicated in Alzheimer's disease and here we present evidence, using a fluorescent antibody to detect gingipain R1 (RgpA), of its presence in a PD population. To further elucidate the action of this gingipain, as well as the action of the lipopolysaccharide (LPS) from , low concentrations of recombinant RgpA and LPS were added to purified fluorescent fibrinogen. We also substantiate previous findings regarding PD by emphasizing the presence of systemic inflammation via multiplex cytokine analysis, and demonstrate hypercoagulation using thromboelastography (TEG), confocal and electron microscopy. Biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. In our PD and control blood analysis, our results show increased hypercoagulation, the presence of amyloid formation in plasma, and profound ultrastructural changes to platelets. Our laboratory analysis of purified fibrinogen with added RgpA, and/or LPS, showed preliminary data with regards to the actions of the protease and the bacterial membrane inflammagen on plasma proteins, to better understand the nature of established PD.
帕金森病(PD)是一种著名的神经退行性疾病,与全身炎症有着密切关联。最近,牙龈蛋白酶组在阿尔茨海默病中的作用受到关注,在此我们提供证据,使用荧光抗体检测牙龈蛋白酶R1(RgpA),证明其在帕金森病患者群体中的存在。为了进一步阐明这种牙龈蛋白酶的作用以及牙龈卟啉单胞菌脂多糖(LPS)的作用,将低浓度的重组RgpA和LPS添加到纯化的荧光纤维蛋白原中。我们还通过多重细胞因子分析强调全身炎症的存在来证实先前关于帕金森病的研究结果,并使用血栓弹力图(TEG)、共聚焦显微镜和电子显微镜证明高凝状态。生物标志物分析证实循环促炎细胞因子水平显著升高。在我们对帕金森病患者和对照者血液的分析中,结果显示高凝状态增加、血浆中存在淀粉样蛋白形成以及血小板有明显的超微结构变化。我们实验室对添加了RgpA和/或LPS的纯化纤维蛋白原的分析,显示了关于该蛋白酶和细菌膜炎症原对血浆蛋白作用的初步数据,以便更好地了解帕金森病的本质。