The status of the terminal regions of α-synuclein in different forms of aggregates during fibrillization
Autor: | Farhang Aliakbari, Mahour Nasouti, Zeinab Alsadat Ahmadi, Amir Tayaranian Marvian, Frederik Lermyte, Hossein Mohammad-Beigi, Joanna F. Collingwood, Sina Mehrpooyan, Dina Morshedi, Daniel E. Otzen |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Amyloid
Alpha-Synuclein 02 engineering and technology Biochemistry Fluorescence Page analysis 03 medical and health sciences chemistry.chemical_compound Structural Biology ddc:570 chemistry [Amyloid] Humans Protein Interaction Domains and Motifs metabolism [Mutant Proteins] metabolism [alpha-Synuclein] Protein terminal labeling Molecular Biology 030304 developmental biology Alpha-synuclein Synucleinopathies 0303 health sciences Fibrillization Chemistry General Medicine 021001 nanoscience & nanotechnology ddc Highly sensitive chemistry [Mutant Proteins] chemistry [alpha-Synuclein] Oligomer Mutation alpha-Synuclein genetics [Mutant Proteins] genetics [alpha-Synuclein] Biophysics Mutant Proteins α synuclein Protein Multimerization 0210 nano-technology |
Zdroj: | Marvian, A T, Aliakbari, F, Mohammad-Beigi, H, Ahmadi, Z A, Mehrpouyan, S, Lermyte, F, Nasouti, M, Collingwood, J F, Otzen, D E & Morshedi, D 2020, ' The status of the terminal regions of α-synuclein in different forms of aggregates during fibrillization ', International Journal of Biological Macromolecules, vol. 155, pp. 543-550 . https://doi.org/10.1016/j.ijbiomac.2020.03.238 International journal of biological macromolecules 155, 543-550 (2020). doi:10.1016/j.ijbiomac.2020.03.238 |
Popis: | 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. |
Databáze: | OpenAIRE |
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