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α-Synuclein aggregation at low concentrations
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SYSNO ASEP 0507378 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title α-Synuclein aggregation at low concentrations Author(s) Afitska, Kseniia (UOCHB-X) ORCID, RID
Fučíková, A. (CZ)
Shvadchak, Volodymyr V. (UOCHB-X) ORCID, RID
Yushchenko, Dmytro A. (UOCHB-X) ORCID, RIDSource Title Biochimica Et Biophysica Acta-Proteins and Proteomics. - : Elsevier - ISSN 1570-9639
Roč. 1867, 7/8 (2019), s. 701-709Number of pages 9 s. Language eng - English Country NL - Netherlands Keywords amyloid fibrils ; kinetics ; fibril disaggregation ; critical concentration ; intermediates ; Kd Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GJ18-06255Y GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support UOCHB-X - RVO:61388963 UT WOS 000472814000003 EID SCOPUS 85065874149 DOI 10.1016/j.bbapap.2019.05.003 Annotation Background: Aggregation of the neuronal protein α-synuclein into amyloid fibrils is a hallmark of Parkinson's disease. The propensity of α-synuclein to aggregate increases with the protein concentration. For the development of efficient inhibitors of α-synuclein aggregation, it is important to know the critical concentration of aggregation (the concentration of monomeric protein, below which the protein does not aggregate). Methods: We performed in vitro aggregation studies of α-synuclein at low concentrations (0.11-20 mu M). Aggregation kinetics was measured by ThT fluorescence. Obtained aggregates were characterized using CD-spectroscopy, fluorescent spectroscopy, dynamic light scattering and AFM imaging. Results: Monomeric α-synuclein at concentrations 0.45 mu M and above was able to bind to fibril ends resulting in fibril growth. At the protein concentrations below 0.4 mu M, monomers did not fibrillize, and fibrils disaggregated. In the absence of seeds, fibrils were formed only at monomer concentrations higher than 10 mu M. At low micromolar concentrations, we observed formation of prefibrillar amyloid aggregates, which are able to induce fibril formation in α-synuclein solutions of high concentrations. Conclusions: The critical concentration of α-synuclein fibril growth is similar to 0.4 mu M. Prefibrillar amyloid aggregates appear at concentrations between 0.45 and 3 mu M and are an intermediate state between monomers and fibrils. Although morphologically different from fibrils, prefibrillar aggregates have similar properties to those of fibrils. General significance: We determined the critical concentration of α-synuclein fibril growth. We showed that fibrils can grow at much lower monomer concentrations than that required for de novo fibril formation. We characterized a prefibrillar intermediate species formed upon aggregation of α-synuclein at low micromolar concentration. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2020 Electronic address https://www.sciencedirect.com/science/article/abs/pii/S1570963919300834?via%3Dihub
Number of the records: 1