TY  - JOUR
AU  - Tayaranian Marvian, Amir
AU  - Aliakbari, Farhang
AU  - Mohammad-Beigi, Hossein
AU  - Ahmadi, Zeinab Alsadat
AU  - Mehrpooyan, Sina
AU  - Lermyte, Frederik
AU  - Nasouti, Mahour
AU  - Collingwood, Joanna F.
AU  - Otzen, Daniel E.
AU  - Morshedi, Dina
TI  - The status of the terminal regions of α-synuclein in different forms of aggregates during fibrillization
JO  - International journal of biological macromolecules
VL  - 155
SN  - 0141-8130
CY  - New York, NY [u.a.]
PB  - Elsevier
M1  - DZNE-2020-01182
SP  - 543-550
PY  - 2020
AB  - 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.
KW  - Amyloid: chemistry
KW  - Humans
KW  - Mutant Proteins: chemistry
KW  - Mutant Proteins: genetics
KW  - Mutant Proteins: metabolism
KW  - Mutation
KW  - Protein Interaction Domains and Motifs
KW  - Protein Multimerization
KW  - alpha-Synuclein: chemistry
KW  - alpha-Synuclein: genetics
KW  - alpha-Synuclein: metabolism
LB  - PUB:(DE-HGF)16
C6  - pmid:32240735
DO  - DOI:10.1016/j.ijbiomac.2020.03.238
UR  - https://pub.dzne.de/record/151598
ER  -