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AuthorZand Z.
AuthorKhaki P.A.
AuthorSalihi A.
AuthorSharifi M.
AuthorNanakali N.M.Q.
AuthorAlasady A.A.B.
AuthorAziz F.M.
AuthorShahpasand K.
AuthorHasan, Anwarul
AuthorFalahati M.
Available date2022-05-21T10:18:33Z
Publication Date2019
Publication NameInternational Journal of Nanomedicine
ResourceScopus
Identifierhttp://dx.doi.org/10.2147/IJN.S220380
URIhttp://hdl.handle.net/10576/31328
AbstractAim: 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 a-syn in amyloidogenic conditions, respectively. Congo red and CD assays demonstrated that CeO2 NPs reduce the formation of amyloid species and ?-sheets structures of a-syn molecules, respectively. TEM investigation also confirmed that CeO2 NPs limited the formation of well-defined fibrillary structures of a- syn molecules. Molecular docking and dynamic studies revealed that CeO2 NPs could bind with different affinities to a-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 a-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.
Languageen
PublisherDove Medical Press Ltd.
SubjectAmyloid
Cellular assay
Cerium oxide
Cytotoxicity
Inhibition
Nanoparticle
Spectroscopy
TitleCerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity
TypeArticle
Volume Number14
dc.accessType Open Access


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