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 (α-syn) amyloid fibril formation as a model of Parkinson's disease in the presence of silica oxide nanoparticles (SiO NPs). Also, different cellular and molecular assays such as MTT, LDH, caspase, ROS, and qPCR were performed to reveal the α-syn amyloid fibrils-associated cytotoxicity against SH-SY5Y cells. Fluorescence measurements showed that SiO NPs accelerate the α-syn aggregation and exposure of hydrophobic moieties. Congo red absorbance, circular dichroism (CD), and transmission electron microscopy (TEM) analysis depicted the SiO NPs accelerated the formation of α-syn amyloid fibrils. Molecular docking study showed that SiO clusters preferably bind to the N-terminal of α-syn as the helix folding site. We also realized that SiO NPs increase the cytotoxicity of α-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 α-syn amyloid fibrils formed in the presence of SiO 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.