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

Research output: Contribution to journalJournal articlepeer-review

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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 articlepeer-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., 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, 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 = jun,
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