Lipopolysaccharide-binding protein (LBP) can reverse the amyloid state of fibrin seen or induced in Parkinson's disease - PubMed (original) (raw)

Lipopolysaccharide-binding protein (LBP) can reverse the amyloid state of fibrin seen or induced in Parkinson's disease

Etheresia Pretorius et al. PLoS One. 2018.

Abstract

The thrombin-induced polymerisation of fibrinogen to form fibrin is well established as a late stage of blood clotting. It is known that Parkinson's Disease (PD) is accompanied by dysregulation in blood clotting, but it is less widely known as a coagulopathy. In recent work, we showed that the presence of tiny amounts of bacterial lipopolysaccharide (LPS) in healthy individuals could cause clots to adopt an amyloid form, and this could be observed via scanning electron microscopy (SEM) or via the fluorescence of thioflavin-T. This could be prevented by the prior addition of lipopolysaccharide-binding protein (LBP). We had also observed by SEM this unusual clotting in the blood of patients with Parkinson's Disease. We hypothesised, and here show, that this too can be prevented by LBP in the context of PD. This adds further evidence implicating inflammatory microbial cell wall products as an accompaniment to the disease, and may be part of its aetiology. This may lead to novel treatment strategies in PD designed to target microbes and their products.

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Conflict of interest statement

Competing Interests: The authors declare the following patent application: Method for treating Parkinson’s Disease (ZA2017/05547).

Figures

Fig 1

Fig 1

A and B) Clot structure from two healthy individuals, imaged in an SEM and showing a ‘normal’ ‘spaghetti’ or ‘noodle’ type of structure. All clots were created by adding thrombin to PPP. C) SEM micrographs of PPP from a Parkinson’s disease individuals with added thrombin, showing a ‘dense matted deposit’; D) PPP from same individual, but exposed to 2ng.L-1 LPS-binding protein followed by addition of thrombin; now showing a structure similar to that of healthy controls.

Fig 2

Fig 2

A): Airyscan micrographs of PPP with added thrombin to form extensive fibrin fibres from an individual with Parkinson’s disease (PD); B) PPP from the same individual, but exposed to 2ng.L-1 LPS-binding protein followed by addition of thrombin. Thioflavin T (ThT) (5 μM) was added before thrombin. Micrographs were taken with a Zeiss LSM 510 META confocal microscope with a Plan-Apochromat 63x/1.4 Oil DIC objective. LBP dramatically reduced the fluorescence seen in samples from patients with PD. Gain settings were kept the same during all data capturing and not changed for statistical analysis, but brightness and contrast was slightly adjusted for fig preparation.

Fig 3

Fig 3. Boxplots of the distribution of the coefficients of variation in the pixel intensities of the SEM and Airyscan clot images.

Fig 4

Fig 4

A and B) Representative histograms of the 8-bit intensity for a representative SEM clot from PPP of an individual with Parkinson’s disease and after addition of LBP, respectively. C and D) Representative histograms of the 8-bit intensity for a typical Airyscan clot from PPP of an individual with Parkinson’s disease and after addition of LBP, respectively.

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Grants and funding

This work was supported by the National Research Foundation grant 91548: Competitive Program and South African Medical Research Council to EP, and the Biotechnology and Biological Sciences Research Council Grant BB/L025752/1 to DBK. Some reagent funds were supplied as a philanthropic gift by an anonymous donor. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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