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Mechanistic Understanding of the Interactions Between Nano-Objects With Different Surface Properties and Α-Synuclein Publisher Pubmed



Mohammadbeigi H1 ; Hosseini A2, 3 ; Adeli M4, 5 ; Ejtehadi MR6, 7 ; Christiansen G8 ; Sahin C1, 9 ; Tu Z5 ; Tavakol M10 ; Dilmaghanimarand A11 ; Nabipour I12 ; Farzadfar F11 ; Otzen DE1, 13 ; Mahmoudi M14 ; Hajipour MJ11, 12
Authors

Source: ACS Nano Published:2019


Abstract

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers. © 2019 American Chemical Society.
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