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

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.

Potential Treatment of Parkinson's Disease, Using Last-Generation Carbon Nanotubes: A Bimolecular In-Silico Study

“…shows the results of this study, and Hossein Mohammad-Beigi et al [32] are in agreement, which validates the results in this study.…”

“…VDW energy in this study and[32] to validate the results4. ResultsFigures3a to 3d show α-synuclein in the simulation with BCN, P-CNT, and N-CNT after 40 nanoseconds, while Figure 3e shows the folded α-synuclein.…”

“…The molecular dynamics of graphene polyglycerol and amyloid in water were simulated by Hossein Mohammad-Beigi et al [32]. Since the force field OPLS and the simulation method LINCS in this article are very similar to Hossein Mohammad-Beigi et al [32], the results of the repeated VDW energy in the same condition were compared to validate the results (Figure 2). This figure…”

“…The most significant instability in the molecular structure of α-synuclein has been performed by P-CNT, which means that P-CNT is the best nanoparticle to prevent amyloid fibrillation. [32], [64]- [66]. The new generation of nanotubes that using from nitrogen and phosphorus dopants, has found significant applications [67]- [69].…”

“…In this study, the functionality of nanoparticles, and various parameters involved in their interactions with α-synuclein proteins have been compared. In order to validate the model employed in this study, the results initially compared with Mohammad-beigi et al [32]. The remainder of the paper is organized into three sections: section two describes the method that was used in this study, results are presented in section three, and the last section concludes the paper.…”