TY - JOUR
T1 - Mechanistic study of the inhibitory activity of Geum urbanum extract against α-Synuclein fibrillation
AU - Lobbens, Eva Stephanie
AU - Breydo, Leonid
AU - Pedersen, Thomas Skamris
AU - Vestergaard, Bente
AU - Jäger, Anna K
AU - Jørgensen, Lene
AU - Uversky, Vladimir
AU - van de Weert, Marco
PY - 2016/6/21
Y1 - 2016/6/21
N2 - 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.
AB - 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.
U2 - 10.1016/j.bbapap.2016.06.009
DO - 10.1016/j.bbapap.2016.06.009
M3 - Journal article
C2 - 27353564
VL - 1864
SP - 1160
EP - 1169
JO - B B A - Proteins and Proteomics
JF - B B A - Proteins and Proteomics
SN - 1570-9639
IS - 9
ER -