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Characteristics of the interaction between different toxic aggregated species of alpha-synuclein and cell membrane

A.T. Marvian, D. Morshedi, F. Aliakbari, H. Ghapani, M. Nasuti (Tehran, Islamic Republic of Iran)

Meeting: 2016 International Congress

Abstract Number: 861

Keywords: Alpha-synuclein, Cell death, Synucleinopathies

Session Information

Date: Tuesday, June 21, 2016

Session Title: Parkinson's disease: Pathophysiology

Session Time: 12:30pm-2:00pm

Location: Exhibit Hall located in Hall B, Level 2

Objective: To determine (1) the interaction rate of each toxic aggregated species of alpha-synuclein (α-Syn) with cell membrane compare to the monomeric form, (2) the role of each end part of α-Syn in the interaction between aggregates and cell membrane.

Background: Amyloid aggregation of α-Syn is the main hallmark of several neurodegenerative diseases called synucleinopathies. A major pathohistological feature of these diseases is the cytoplasmic inclusions known as lewy bodies or lewy neurites which mainly consist of α-Syn aggregates. Many efforts depicted the strong impact of the α-Syn aggregates on defecting cellular membrane and its role on cell death induction; however, the exact mechanism of this phenomenon is still elusive.

Methods: Here in, we analyzed the both end parts of α-Syn to elucidate the role of each region in the monomeric, oligomeric and fibrillar forms in the interaction with neuronal cell membrane, using site-directed fluorescent labeled α-Syn. Interaction and cytotoxicity analysis were implemented on two neuroblastoma cell lines including PC12 and SH-SY5Y.

Results: Our results illustrating the high affinity of α-Syn intermediate aggregates and fibrillar structures to cell membrane compared to the monomeric form, associated with their cell death inducing effect. Interestingly, fluorescence analysis of end parts of the protein revealed the critical role of C-terminal region on the interaction of oligomeric structures with cell membrane.

Conclusions: These data together highlight the importance of studying on the N and C terminals of α-Syn and their roles in protein interactions with membranes in order to have a complete perspective on different aspects of α-Syn / cellular membrane interaction which have critical role on the α-Syn cytotoxicity and also activity. Therefore, having a comprehensive overview on the role of each part of α-Syn in the process of neurodegeneration will pave the way for further therapeutic findings and drug discoveries.

To cite this abstract in AMA style:

A.T. Marvian, D. Morshedi, F. Aliakbari, H. Ghapani, M. Nasuti. Characteristics of the interaction between different toxic aggregated species of alpha-synuclein and cell membrane [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/characteristics-of-the-interaction-between-different-toxic-aggregated-species-of-alpha-synuclein-and-cell-membrane/. Accessed May 14, 2025.
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