4.6 Article

Parkinson's Disease: A Systemic Inflammatory Disease Accompanied by Bacterial Inflammagens

Journal

FRONTIERS IN AGING NEUROSCIENCE
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2019.00210

Keywords

Parkinson's disease; systemic inflammation; cytokines; LPS from Porphyromonas gingivalis; gingipains; amyloid formation

Funding

  1. Biotechnology and Biological Sciences Research Council [BB/L025752/1]
  2. National Research Foundation (NRF) of South Africa [91548]
  3. Medical Research Council of South Africa (MRC
  4. Self-Initiated Research Program)
  5. BBSRC [BB/L025752/1] Funding Source: UKRI

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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 Porphyromonas gingivalis 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 P. 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.

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