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المؤلفZand Z.
المؤلفKhaki P.A.
المؤلفSalihi A.
المؤلفSharifi M.
المؤلفNanakali N.M.Q.
المؤلفAlasady A.A.B.
المؤلفAziz F.M.
المؤلفShahpasand K.
المؤلفHasan, Anwarul
المؤلفFalahati M.
تاريخ الإتاحة2022-05-21T10:18:33Z
تاريخ النشر2019
اسم المنشورInternational Journal of Nanomedicine
المصدرScopus
المعرّفhttp://dx.doi.org/10.2147/IJN.S220380
معرّف المصادر الموحدhttp://hdl.handle.net/10576/31328
الملخصAim: 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.
اللغةen
الناشرDove Medical Press Ltd.
الموضوعAmyloid
Cellular assay
Cerium oxide
Cytotoxicity
Inhibition
Nanoparticle
Spectroscopy
العنوانCerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity
النوعArticle
رقم المجلد14
dc.accessType Open Access


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