The status of the terminal regions of α-synuclein in different forms of aggregates during fibrillization.

Autor: Marvian AT; Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; Department of Neurology, School of Medicine, Technical University of Munich, Munich, Germany; Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany., Aliakbari F; Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; Interdisciplinary Nanoscience Centre (iNANO), Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark., Mohammad-Beigi H; Interdisciplinary Nanoscience Centre (iNANO), Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark., Ahmadi ZA; Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran., Mehrpooyan S; Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran., Lermyte F; School of Engineering, University of Warwick, Coventry, UK., Nasouti M; Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran., Collingwood JF; School of Engineering, University of Warwick, Coventry, UK., Otzen DE; Interdisciplinary Nanoscience Centre (iNANO), Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark., Morshedi D; Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address: morshedi@nigeb.ac.ir.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2020 Jul 15; Vol. 155, pp. 543-550. Date of Electronic Publication: 2020 Mar 31.
DOI: 10.1016/j.ijbiomac.2020.03.238
Abstrakt: The α-synuclein (αSN) amyloid fibrillization process is known to be a crucial phenomenon associated with neuronal loss in various neurodegenerative diseases, most famously Parkinson's disease. The process involves different aggregated species and ultimately leads to formation of β-sheet rich fibrillar structures. Despite the essential role of αSN aggregation in the pathoetiology of various neurological disorders, the characteristics of various assemblies are not fully understood. Here, we established a fluorescence-based model for studying the end-parts of αSN to decipher the structural aspects of aggregates during the fibrillization. Our model proved highly sensitive to the events at the early stage of the fibrillization process, which are hardly detectable with routine techniques. Combining fluorescent and PAGE analysis, we found different oligomeric aggregates in the nucleation phase of fibrillization with different sensitivity to SDS and different structures based on αSN termini. Moreover, we found that these oligomers are highly dynamic: after reaching peak levels during fibrillization, they decline and eventually disappear, suggesting their transformation into other αSN aggregated species. These findings shed light on the structural features of various αSN aggregates and their dynamics in synucleinopathies.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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