Mechanistic study of the inhibitory activity of Geum urbanum extract against α-Synuclein fibrillation

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Mechanistic study of the inhibitory activity of Geum urbanum extract against α-Synuclein fibrillation. / Lobbens, Eva Stephanie; Breydo, Leonid; Pedersen, Thomas Skamris; Vestergaard, Bente; Jäger, Anna K; Jørgensen, Lene; Uversky, Vladimir ; van de Weert, Marco.

In: B B A - Proteins and Proteomics, Vol. 1864, No. 9, 21.06.2016, p. 1160-1169.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Lobbens, ES, Breydo, L, Pedersen, TS, Vestergaard, B, Jäger, AK, Jørgensen, L, Uversky, V & van de Weert, M 2016, 'Mechanistic study of the inhibitory activity of Geum urbanum extract against α-Synuclein fibrillation', B B A - Proteins and Proteomics, vol. 1864, no. 9, pp. 1160-1169. https://doi.org/10.1016/j.bbapap.2016.06.009

APA

Lobbens, E. S., Breydo, L., Pedersen, T. S., Vestergaard, B., Jäger, A. K., Jørgensen, L., ... van de Weert, M. (2016). Mechanistic study of the inhibitory activity of Geum urbanum extract against α-Synuclein fibrillation. B B A - Proteins and Proteomics, 1864(9), 1160-1169. https://doi.org/10.1016/j.bbapap.2016.06.009

Vancouver

Lobbens ES, Breydo L, Pedersen TS, Vestergaard B, Jäger AK, Jørgensen L et al. Mechanistic study of the inhibitory activity of Geum urbanum extract against α-Synuclein fibrillation. B B A - Proteins and Proteomics. 2016 Jun 21;1864(9):1160-1169. https://doi.org/10.1016/j.bbapap.2016.06.009

Author

Lobbens, Eva Stephanie ; Breydo, Leonid ; Pedersen, Thomas Skamris ; Vestergaard, Bente ; Jäger, Anna K ; Jørgensen, Lene ; Uversky, Vladimir ; van de Weert, Marco. / Mechanistic study of the inhibitory activity of Geum urbanum extract against α-Synuclein fibrillation. In: B B A - Proteins and Proteomics. 2016 ; Vol. 1864, No. 9. pp. 1160-1169.

Bibtex

@article{96a63d47f06f4fe3a7a2b929a67d4711,
title = "Mechanistic study of the inhibitory activity of Geum urbanum extract against α-Synuclein fibrillation",
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.",
author = "Lobbens, {Eva Stephanie} and Leonid Breydo and Pedersen, {Thomas Skamris} and Bente Vestergaard and J{\"a}ger, {Anna K} and Lene J{\o}rgensen and Vladimir Uversky and {van de Weert}, Marco",
year = "2016",
month = "6",
day = "21",
doi = "10.1016/j.bbapap.2016.06.009",
language = "English",
volume = "1864",
pages = "1160--1169",
journal = "B B A - Proteins and Proteomics",
issn = "1570-9639",
publisher = "Elsevier",
number = "9",

}

RIS

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 -

ID: 163158518