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

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  • Amir Tayaranian Marvian, National Institute of Genetic Engineering and Biotechnology, Technical University of Munich, German Center for Neurodegenerative Diseases
  • ,
  • Farhang Aliakbari, National Institute of Genetic Engineering and Biotechnology
  • ,
  • Hossein Mohammad-Beigi
  • Zeinab Alsadat Ahmadi, National Institute of Genetic Engineering and Biotechnology
  • ,
  • Sina Mehrpouyan, National Institute of Genetic Engineering and Biotechnology
  • ,
  • Frederik Lermyte, University of Warwick
  • ,
  • Mahour Nasouti, National Institute of Genetic Engineering and Biotechnology
  • ,
  • Joanna F Collingwood, University of Warwick
  • ,
  • Daniel E Otzen
  • Dina Morshedi, National Institute of Genetic Engineering and Biotechnology

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.

Original languageEnglish
JournalInternational Journal of Biological Macromolecules
Volume155
Pages (from-to)543-550
Number of pages8
ISSN0141-8130
DOIs
Publication statusPublished - Jul 2020

    Research areas

  • Alpha-Synuclein, Fibrillization, Fluorescence, Oligomer, Protein terminal labeling

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