Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth. / Pedersen, Martin Nors; Foderà, Vito; Horvath, Istvan; van Maarschalkerweerd, Andreas; Nørgaard Toft, Katrine; Weise, Christoph; Almqvist, Fredrik; Wolf-Watz, Magnus; Wittung-Stafshede, Pernilla; Vestergaard, Bente.

In: Scientific Reports, Vol. 5, 10422, 2015, p. 1-12.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Pedersen, MN, Foderà, V, Horvath, I, van Maarschalkerweerd, A, Nørgaard Toft, K, Weise, C, Almqvist, F, Wolf-Watz, M, Wittung-Stafshede, P & Vestergaard, B 2015, 'Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth', Scientific Reports, vol. 5, 10422, pp. 1-12. https://doi.org/10.1038/srep10422

APA

Pedersen, M. N., Foderà, V., Horvath, I., van Maarschalkerweerd, A., Nørgaard Toft, K., Weise, C., Almqvist, F., Wolf-Watz, M., Wittung-Stafshede, P., & Vestergaard, B. (2015). Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth. Scientific Reports, 5, 1-12. [10422]. https://doi.org/10.1038/srep10422

Vancouver

Pedersen MN, Foderà V, Horvath I, van Maarschalkerweerd A, Nørgaard Toft K, Weise C et al. Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth. Scientific Reports. 2015;5:1-12. 10422. https://doi.org/10.1038/srep10422

Author

Pedersen, Martin Nors ; Foderà, Vito ; Horvath, Istvan ; van Maarschalkerweerd, Andreas ; Nørgaard Toft, Katrine ; Weise, Christoph ; Almqvist, Fredrik ; Wolf-Watz, Magnus ; Wittung-Stafshede, Pernilla ; Vestergaard, Bente. / Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth. In: Scientific Reports. 2015 ; Vol. 5. pp. 1-12.

Bibtex

@article{c1ab11f7599841479f5995991feca8ef,
title = "Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth",
abstract = "Aggregation of proteins into amyloid deposits is the hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The suggestion that intermediate oligomeric species may be cytotoxic has led to intensified investigations of pre-fibrillar oligomers, which are complicated by their transient nature and low population. Here we investigate alpha-synuclein oligomers, enriched by a 2-pyridone molecule (FN075), and the conversion of oligomers into fibrils. As probed by leakage assays, the FN075 induced oligomers potently disrupt vesicles in vitro, suggesting a potential link to disease related degenerative activity. Fibrils formed in the presence and absence of FN075 are indistinguishable on microscopic and macroscopic levels. Using small angle X-ray scattering, we reveal that FN075 induced oligomers are similar, but not identical, to oligomers previously observed during alpha-synuclein fibrillation. Since the levels of FN075 induced oligomers correlate with the amounts of fibrils among different FN075:protein ratios, the oligomers appear to be on-pathway and modeling supports an 'oligomer stacking model' for alpha-synuclein fibril elongation.",
keywords = "Alzheimer Disease, Amyloid, Amyloidogenic Proteins, Humans, Ligands, Parkinson Disease, Protein Aggregation, Pathological, Protein Structure, Secondary, Pyridones, alpha-Synuclein",
author = "Pedersen, {Martin Nors} and Vito Foder{\`a} and Istvan Horvath and {van Maarschalkerweerd}, Andreas and {N{\o}rgaard Toft}, Katrine and Christoph Weise and Fredrik Almqvist and Magnus Wolf-Watz and Pernilla Wittung-Stafshede and Bente Vestergaard",
year = "2015",
doi = "10.1038/srep10422",
language = "English",
volume = "5",
pages = "1--12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth

AU - Pedersen, Martin Nors

AU - Foderà, Vito

AU - Horvath, Istvan

AU - van Maarschalkerweerd, Andreas

AU - Nørgaard Toft, Katrine

AU - Weise, Christoph

AU - Almqvist, Fredrik

AU - Wolf-Watz, Magnus

AU - Wittung-Stafshede, Pernilla

AU - Vestergaard, Bente

PY - 2015

Y1 - 2015

N2 - Aggregation of proteins into amyloid deposits is the hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The suggestion that intermediate oligomeric species may be cytotoxic has led to intensified investigations of pre-fibrillar oligomers, which are complicated by their transient nature and low population. Here we investigate alpha-synuclein oligomers, enriched by a 2-pyridone molecule (FN075), and the conversion of oligomers into fibrils. As probed by leakage assays, the FN075 induced oligomers potently disrupt vesicles in vitro, suggesting a potential link to disease related degenerative activity. Fibrils formed in the presence and absence of FN075 are indistinguishable on microscopic and macroscopic levels. Using small angle X-ray scattering, we reveal that FN075 induced oligomers are similar, but not identical, to oligomers previously observed during alpha-synuclein fibrillation. Since the levels of FN075 induced oligomers correlate with the amounts of fibrils among different FN075:protein ratios, the oligomers appear to be on-pathway and modeling supports an 'oligomer stacking model' for alpha-synuclein fibril elongation.

AB - Aggregation of proteins into amyloid deposits is the hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The suggestion that intermediate oligomeric species may be cytotoxic has led to intensified investigations of pre-fibrillar oligomers, which are complicated by their transient nature and low population. Here we investigate alpha-synuclein oligomers, enriched by a 2-pyridone molecule (FN075), and the conversion of oligomers into fibrils. As probed by leakage assays, the FN075 induced oligomers potently disrupt vesicles in vitro, suggesting a potential link to disease related degenerative activity. Fibrils formed in the presence and absence of FN075 are indistinguishable on microscopic and macroscopic levels. Using small angle X-ray scattering, we reveal that FN075 induced oligomers are similar, but not identical, to oligomers previously observed during alpha-synuclein fibrillation. Since the levels of FN075 induced oligomers correlate with the amounts of fibrils among different FN075:protein ratios, the oligomers appear to be on-pathway and modeling supports an 'oligomer stacking model' for alpha-synuclein fibril elongation.

KW - Alzheimer Disease

KW - Amyloid

KW - Amyloidogenic Proteins

KW - Humans

KW - Ligands

KW - Parkinson Disease

KW - Protein Aggregation, Pathological

KW - Protein Structure, Secondary

KW - Pyridones

KW - alpha-Synuclein

U2 - 10.1038/srep10422

DO - 10.1038/srep10422

M3 - Journal article

C2 - 26020724

VL - 5

SP - 1

EP - 12

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 10422

ER -

ID: 161863000