Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein

Hossein Mohammad-Beigi, Atiyeh Hosseini, Mohsen Adeli, Mohammad Reza Ejtehadi, Gunna Christiansen, Cagla Sahin, Zhaoxu Tu, Mahdi Tavakol, Arezou Dilmaghani-Marand, Iraj Nabipour, Farshad Farzadfar, Daniel Erik Otzen, Morteza Mahmoudi, Mohammad Javad Hajipour

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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.

OriginalsprogEngelsk
TidsskriftACS Nano
Vol/bind13
Nummer3
Sider (fra-til)3243-3256
Antal sider14
ISSN1936-0851
DOI
StatusUdgivet - 2019

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