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 a- synuclein (a-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 a-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 α-syn in amyloidogenic conditions, respectively. Congo red and CD assays demonstrated that CeO₂ NPs reduce the formation of amyloid species and Β-sheets structures of α-syn molecules, respectively. TEM investigation also confirmed that CeO₂ NPs limited the formation of well-defined fibrillary structures of α- syn molecules. Molecular docking and dynamic studies revealed that CeO₂ NPs could bind with different affinities to α-syn monomer and amyloid species and fibrillar structure of a-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 α-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.