Mechanistic Study of the Inhibitory Activity of Geum Urbanum Extract against Α-Synuclein Fibrillation
Digital Object Identifier (DOI)
The presence of Lewy bodies and Lewy neurites is a major pathological hallmark of Parkinson's disease and is hypothesized to be linked to disease development, although this is not yet conclusive. Lewy bodies and Lewy neurites primarily consist of fibrillated α-Synuclein; yet, there is no treatment available targeting stabilization of α-Synuclein in its native state. The aim of the present study was to investigate the inhibitory activity of an ethanolic extract of Geum urbanum against α-Synuclein fibrillation and examine the structural changes of α-Synuclein in the presence of the extract. The anti-fibrillation and anti-aggregation activities of the plant extract were monitored by thioflavin T fibrillation assays and size exclusion chromatography, while structural changes were followed by circular dichroism, Fourier transform infrared spectroscopy, intrinsic fluorescence, small angle X-ray scattering and electron microscopy. Since the extract is a complex mixture, structure-function relationships could not be determined. Under the experimental conditions investigated, Geum urbanum was found to inhibit α-Synuclein fibrillation in a concentration dependent way, and to partly disintegrate preformed α-Synuclein fibrils. Based on the structural changes of α-Synuclein in the presence of extract, we propose that Geum urbanum delays α-Synuclein fibrillation either by reducing the fibrillation ability of one or more of the aggregation prone intermediates or by directing α-Synuclein aggregation towards a non-fibrillar state. However, whether these alterations of the fibrillation pathway lead to less pathogenic species is yet to be determined.
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Citation / Publisher Attribution
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, v. 1864, issue 9, p. 1160-1169
Scholar Commons Citation
Lobbens, Eva S.; Breydo, Leonid; Skamris, Thomas; Vestergaard, Bente; Jäger, Anna K.; Jorgensen, Lene; Uversky, Vladimir; and van de Weert, Marco, "Mechanistic Study of the Inhibitory Activity of Geum Urbanum Extract against Α-Synuclein Fibrillation" (2016). Molecular Medicine Faculty Publications. 355.