Parkinson's disease: a systemic inflammatory disease accompanied by bacterial inflammagens
Parkinson's disease: a systemic inflammatory disease accompanied by bacterial inflammagens
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帕金森病：一种伴有细菌性炎症原的全身炎症性疾病
DOI：
10.1101/646307
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Adams B
中科院分区：
文献类型：
--
作者：
Adams B
帕金森病 (PD) 是一种众所周知的神经退行性疾病，与全身炎症密切相关。最近，来自牙龈卟啉单胞菌的牙龈蛋白酶组的作用与阿尔茨海默氏病有关，在这里，我们使用荧光抗体检测牙龈蛋白酶 R1 (RgpA)，证明其在帕金森病人群中的存在。为了进一步阐明这种牙龈蛋白酶的作用，以及来自 P. 的脂多糖 (LPS) 的作用。在纯化的荧光纤维蛋白原中添加低浓度的重组 RgpA 和 LPS。我们还通过多重细胞因子分析强调全身炎症的存在，证实了先前关于 PD 的发现，并使用血栓弹力图 (TEG)、共聚焦和电子显微镜证明了高凝状态。生物标志物分析证实循环促炎细胞因子水平显着升高。在我们的 PD 和对照血液分析中，我们的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的深刻超微结构变化。我们对添加 RgpA 和/或 LPS 的纯化纤维蛋白原进行实验室分析，显示了有关蛋白酶和细菌膜炎症原对血浆蛋白的作用的初步数据，以更好地了解已建立的 PD 的性质。
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 fromPorphyromonas gingivaliswas 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) fromP. gingivalis, 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.