Mechanistic Study of the Inhibitory Activity of Geum Urbanum Extract against Α-Synuclein Fibrillation
Document Type
Article
Publication Date
2016
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.bbapap.2016.06.009
Abstract
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.
Was this content written or created while at USF?
Yes
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.
https://digitalcommons.usf.edu/mme_facpub/355
