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Quantitative thermophoretic study of disease-related protein aggregates

Amyloid fibrils are a hallmark of a range of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. A detailed understanding of the physico-chemical properties of the different aggregated forms of proteins, and of their interactions with other compounds of diagnostic or therape...

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Autores principales: Wolff , Manuel, Mittag, Judith J., Herling, Therese W., Genst, Erwin De, Dobson, Christopher M., Knowles, Tuomas P. J., Braun, Dieter, Buell, Alexander K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794802/
https://www.ncbi.nlm.nih.gov/pubmed/26984748
http://dx.doi.org/10.1038/srep22829
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author Wolff , Manuel
Mittag, Judith J.
Herling, Therese W.
Genst, Erwin De
Dobson, Christopher M.
Knowles, Tuomas P. J.
Braun, Dieter
Buell, Alexander K.
author_facet Wolff , Manuel
Mittag, Judith J.
Herling, Therese W.
Genst, Erwin De
Dobson, Christopher M.
Knowles, Tuomas P. J.
Braun, Dieter
Buell, Alexander K.
author_sort Wolff , Manuel
collection PubMed
description Amyloid fibrils are a hallmark of a range of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. A detailed understanding of the physico-chemical properties of the different aggregated forms of proteins, and of their interactions with other compounds of diagnostic or therapeutic interest, is crucial for devising effective strategies against such diseases. Protein aggregates are situated at the boundary between soluble and insoluble structures, and are challenging to study because classical biophysical techniques, such as scattering, spectroscopic and calorimetric methods, are not well adapted for their study. Here we present a detailed characterization of the thermophoretic behavior of different forms of the protein α-synuclein, whose aggregation is associated with Parkinson’s disease. Thermophoresis is the directed net diffusional flux of molecules and colloidal particles in a temperature gradient. Because of their low volume requirements and rapidity, analytical methods based on this effect have considerable potential for high throughput screening for drug discovery. In this paper we rationalize and describe in quantitative terms the thermophoretic behavior of monomeric, oligomeric and fibrillar forms of α-synuclein. Furthermore, we demonstrate that microscale thermophoresis (MST) is a valuable method for screening for ligands and binding partners of even such highly challenging samples as supramolecular protein aggregates.
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spelling pubmed-47948022016-03-18 Quantitative thermophoretic study of disease-related protein aggregates Wolff , Manuel Mittag, Judith J. Herling, Therese W. Genst, Erwin De Dobson, Christopher M. Knowles, Tuomas P. J. Braun, Dieter Buell, Alexander K. Sci Rep Article Amyloid fibrils are a hallmark of a range of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. A detailed understanding of the physico-chemical properties of the different aggregated forms of proteins, and of their interactions with other compounds of diagnostic or therapeutic interest, is crucial for devising effective strategies against such diseases. Protein aggregates are situated at the boundary between soluble and insoluble structures, and are challenging to study because classical biophysical techniques, such as scattering, spectroscopic and calorimetric methods, are not well adapted for their study. Here we present a detailed characterization of the thermophoretic behavior of different forms of the protein α-synuclein, whose aggregation is associated with Parkinson’s disease. Thermophoresis is the directed net diffusional flux of molecules and colloidal particles in a temperature gradient. Because of their low volume requirements and rapidity, analytical methods based on this effect have considerable potential for high throughput screening for drug discovery. In this paper we rationalize and describe in quantitative terms the thermophoretic behavior of monomeric, oligomeric and fibrillar forms of α-synuclein. Furthermore, we demonstrate that microscale thermophoresis (MST) is a valuable method for screening for ligands and binding partners of even such highly challenging samples as supramolecular protein aggregates. Nature Publishing Group 2016-03-17 /pmc/articles/PMC4794802/ /pubmed/26984748 http://dx.doi.org/10.1038/srep22829 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Wolff , Manuel
Mittag, Judith J.
Herling, Therese W.
Genst, Erwin De
Dobson, Christopher M.
Knowles, Tuomas P. J.
Braun, Dieter
Buell, Alexander K.
Quantitative thermophoretic study of disease-related protein aggregates
title Quantitative thermophoretic study of disease-related protein aggregates
title_full Quantitative thermophoretic study of disease-related protein aggregates
title_fullStr Quantitative thermophoretic study of disease-related protein aggregates
title_full_unstemmed Quantitative thermophoretic study of disease-related protein aggregates
title_short Quantitative thermophoretic study of disease-related protein aggregates
title_sort quantitative thermophoretic study of disease-related protein aggregates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794802/
https://www.ncbi.nlm.nih.gov/pubmed/26984748
http://dx.doi.org/10.1038/srep22829
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