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

ACS Nano
Hossein Mohammad-BeigiMohammad Javad Hajipour

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.

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Citations

Sep 29, 2020·International Journal of Nanomedicine·Ehsan AlimohammadiMilad Rezaian
Dec 4, 2020·Journal of Drug Targeting·Panoraia I SiafakaNeslihan Üstündağ Okur
Dec 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mariapina D'OnofrioMichael Assfalg
Mar 12, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Zeinab SouriShabnam Sattari
Mar 16, 2021·The Journal of Physical Chemistry. B·Sarah-Beth T A AmosMark S P Sansom
Apr 23, 2021·Chembiochem : a European Journal of Chemical Biology·Reza MalekiMohammad-Ali Shahbazi
Jun 5, 2021·Journal of Biomedical Nanotechnology·Heping WangXue Xue
Jun 7, 2021·Biochimica Et Biophysica Acta. General Subjects·A AntosovaZ Gazova

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