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 αsynuclein (α-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 α-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 αsyn 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 α-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.