Cerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity

Aim: Among therapeutic proposals for amyloid-associated disorders, special attention has been given to the exploitation of nanoparticles (NPs) as promising agents against aggregation. Methods: In this paper, the inhibitory effect of cerium oxide (CeO2) NPs against alpha-synuclein (alpha-syn) amyloid formation was explored by different methods such as Thioflavin T (ThT) and 8-anilinonaphthalene- 1 -sulfonic acid (ANS) fluorescence spectroscopy, Congo red adsorption assay, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and bioinformatical approaches. Also, the cytotoxicity of alpha-syn amyloid either alone or with CeO2 NPs against neuron-like cells (SH-SY5Y) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and quantitative real-time polymerase chain reaction (Bax and Bcl-2 gene expression) assays. Results: ThT and ANS fluorescence assays indicated that CeO2 NPs inhibit the formation of aggregated species and hydrophobic patches of alpha-syn in amyloidogenic conditions, respectively. Congo red and CD assays demonstrated that CeO2 NPs reduce the formation of amyloid species and beta-sheets structures of alpha-syn molecules, respectively. TEM investigation also confirmed that CeO2 NPs limited the formation of well-defined fibrillary structures of alpha-syn molecules. Molecular docking and dynamic studies revealed that CeO2 NPs could bind with different affinities to alpha-syn monomer and amyloid species and fibrillar structure of alpha-syn is disaggregated in the presence of CeO2 NPs. Moreover, cellular assays depicted that CeO2 NPs mitigate the cell mortality, apoptosis, and the ratio of Bax/Bcl-2 gene expression associated with alpha-syn amyloids. Conclusion: It may be concluded that CeO2 NPs can be used as therapeutic agents to reduce the aggregation of proteins and mitigate the occurrence of neurodegenerative diseases.