Acceleration of α-synuclein fibril formation and associated cytotoxicity stimulated by silica nanoparticles as a model of neurodegenerative diseases

A wide range of biophysical and theoretical analysis were employed to explore the formation of (alpha-syn) amyloid fibril formation as a model of Parkinson's disease in the presence of silica oxide nanoparticles (SiO2 NPs). Also, different cellular and molecular assays such as MTT, LDH, caspase, ROS, and qPCR were performed to reveal the alpha-syn amyloid fibrils-associated cytotoxicity against SH-SY5Y cells. Fluorescence measurements showed that SiO2 NPs accelerate the alpha-syn aggregation and exposure of hydrophobicmoieties. Congo red absorbance, circular dichroism (CD), and transmission electron microscopy (TEM) analysis depicted the SiO2 NPs accelerated the formation of alpha-syn amyloid fibrils. Molecular docking study showed that SiO2 clusters preferably bind to the N-terminal of alpha-syn as the helix folding site. We also realized that SiO2 NPs increase the cytotoxicity of alpha-syn amyloid fibrils through a significant decrease in cell viability, increase in membrane leakage, activation of caspase-9 and -3, elevation of ROS, and increase in the ratio of Bax/Bcl2 mRNA. The cellular assay indicated that alpha-syn amyloid fibrils formed in the presence of SiO2 NPs induce their cytotoxic effects through the mitochondrial-mediated intrinsic apoptosis pathway. We concluded that these data may reveal some adverse effects of NPs on the progression of Parkinson's disease. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

The study demonstrated that SiO2 NPs can accelerate the formation of α-syn amyloid fibrils and increase their cytotoxicity. Experimental results indicate that SiO2 NPs induce the cytotoxic effects of α-syn amyloid fibrils through the mitochondrial-mediated intrinsic apoptosis pathway.