Journal Article

DZNE-2020-01182

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The status of the terminal regions of α-synuclein in different forms of aggregates during fibrillization

Tayaranian Marvian, A. (First author)DZNE* ; Aliakbari, F. ; Mohammad-Beigi, H. ; Ahmadi, Z. A. ; Mehrpooyan, S. ; Lermyte, F. ; Nasouti, M. ; Collingwood, J. F. ; Otzen, D. E. ; Morshedi, D. (Corresponding author)

2020
Elsevier New York, NY [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ijbiomac.2020.03.238

Abstract: 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.

Keyword(s): Amyloid: chemistry (MeSH) ; Humans (MeSH) ; Mutant Proteins: chemistry (MeSH) ; Mutant Proteins: genetics (MeSH) ; Mutant Proteins: metabolism (MeSH) ; Mutation (MeSH) ; Protein Interaction Domains and Motifs (MeSH) ; Protein Multimerization (MeSH) ; alpha-Synuclein: chemistry (MeSH) ; alpha-Synuclein: genetics (MeSH) ; alpha-Synuclein: metabolism (MeSH)

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Contributing Institute(s):

1. Translational Neurodegeneration (AG Höglinger 1 ; AG Höglinger 1)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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