<p>Cerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity</p>

Abstract

AimAmong therapeutic proposals for amyloid-associated disorders, special attention has been given to the exploitation of nanoparticles (NPs) as promising agents against aggregation.MethodsIn this paper, the inhibitory effect of cerium oxide (CeO2) NPs against α-synuclein (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.ResultsThT 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 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.ConclusionIt 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.

Cerium Oxide Nanoparticles Rescue α-Synuclein-Induced Toxicity in a Yeast Model of Parkinson’s Disease

“…Dot blot analysis showed the presence of α-syn in the fractions adsorbed to the CeO 2 NP surface, indicating a direct interaction between CeO 2 NPs and α-syn. These results agree with recently published papers which show how CeO 2 NPs have the best fitting for the active site of α-syn using a computational approach [52,66].…”

“…Since the N-terminal domain and NAC region are necessary for initiating the α-syn misfolding, small molecules (as CeO 2 NPs) that are capable of stabilizing the physiological α-helical vesicle-bound conformation of α-syn might interfere with its pathogenic aggregation [13,94]. Docking studies [52,66] showed that CeO 2 NPs exhibit excellent interactions with crucial residues of the N-terminal membrane-bound domain of α-syn, and it is possible that the interaction with this domain can prevent the conformational changes leading to misfolding and aggregation of α-syn. Further studies are required to better elucidate this issue, but the present work shows how the use of a simplified model of PD can be informative to assess the anti-aggregation properties of small molecules and better understand how α-syn aggregates can acquire their neurotoxic properties and interact with metabolic pathways.…”

“…Cerium oxide nanoparticles (CeO 2 NPs) have gained great interest in cancer treatment [37][38][39][40][41][42], protection from ionizing radiation [43,44], prevention of retinal degeneration [45] and neurodegenerative diseases [46][47][48][49][50][51][52]. Together with a high biocompatibility [53,54], CeO 2 NPs are redox-active materials mimicking enzymes involved in oxidative stress response as superoxide dismutase [55,56] or catalase [57] and, as such, can scavenge ROS and nitric oxide [58].…”

“…However, CeO 2 NPs have been also found to display oxidase-like activity at acidic pH [62] and to generate noxious ROS in different organisms and cell systems [63][64][65]. Recently, docking studies revealed that, compared with other nanostructured materials, CeO 2 NPs best fit in the active site of α-syn and interfere with the formation of fibrillar structures of α-syn formed in vitro [52,66]. Therefore, the aim of the present work was to evaluate the effects of CeO 2 NPs on α-syn toxicity in a validated yeast model that allows us to investigate whether these NPs affect the formation, accumulation and cellular localization of α-syn in vivo, restoring the molecular pathways altered by α-syn overexpression.…”

<p>Cerium Oxide Nanoparticles Regulate Osteoclast Differentiation Bidirectionally by Modulating the Cellular Production of Reactive Oxygen Species</p>

“…In most reports, CeO 2 NPs scavenge reactive oxygen species (ROS), including hydrogen peroxide and free radicals, such as•OH, O 2-,•NO, within the cellular environment, thus attenuating ROS production and organ dysfunction in ROS-related diseases, including myocardial damage, systemic inflammatory reaction syndrome, psoriasis and Alzheimer's disease. [10][11][12][13][14] However, there are also other reports demonstrating that in some acidic environments, such as cancer cells, CeO 2 NPs exhibit oxidase-like activity, enhancing intracellular ROS production and cell toxicity. [15][16][17] In recent years, many researchers have explored the application of CeO 2 NPs in bone regeneration and bone tissue engineering.…”