Over the last decades, cerium oxide nanoparticles (CeO₂ NPs) have gained great interest due to their potential applications, mainly in the fields of agriculture and biomedicine. Promising effects of CeO₂ NPs are recently shown in some neurodegenerative diseases, but the mechanism of action of these NPs in Parkinson’s disease (PD) remains to be investigated. This issue is addressed in the present study by using a yeast model based on the heterologous expression of the human α-synuclein (α-syn), the major component of Lewy bodies, which represent a neuropathological hallmark of PD. We observed that CeO₂ NPs strongly reduce α-syn-induced toxicity in a dose-dependent manner. This effect is associated with the inhibition of cytoplasmic α-syn foci accumulation, resulting in plasma membrane localization of α-syn after NP treatment. Moreover, CeO₂ NPs counteract the α-syn-induced mitochondrial dysfunction and decrease reactive oxygen species (ROS) production in yeast cells. In vitro binding assay using cell lysates showed that α-syn is adsorbed on the surface of CeO₂ NPs, suggesting that these NPs may act as a strong inhibitor of α-syn toxicity not only acting as a radical scavenger, but through a direct interaction with α-syn in vivo.

Engineered nanoparticles (ENPs) have found applications in different fields varying from medical science to electronics. The increasing interest in these materials, fuelled by the potential benefits of their use, has not as yet been matched by a concerted effort to gain a full understanding of potential negative effects they may have on the environment and on human health. In a biological environment, ENPs become coated by a so-called “protein corona”, the structure of which defines their biological identity. The present research set out to characterize the interaction between cadmium sulphide quantum dots (QDs) and yeast cells, isolating and identifying the set of proteins which were adsorbed on the QD surface using liquid chromatography-mass spectrometry followed by an in silico protein analysis. Ring-shaped proteins were particularly prone to binding, and electrostatic and hydrophobic interactions were central for this interaction. QDs strongly increased the transcript levels of genes encoding the major hard corona proteins indicating a mechanism of genetic compensation in response to the “physical sequestration” of these proteins in the QD corona in vivo. The toxicological implications of the protein corona formation were explored using yeast mutant strains carrying deletions in genes encoding the corona proteins. Interestingly, these mutants were tolerant to doses of QDs that were lethal to wild type cells. These results reveal that the hard protein corona mediates the toxicity of QDs in yeast and a major resolution of this interaction at the molecular level is crucial for a better understanding of the in vivo response of ENPs.

Previous work has demonstrated that precipitated (NM-200) and pyrogenic (NM-203) Amorphous Silica Nanoparticles (ASNPs) elicit the inflammatory activation of murine macrophages, with more pronounced effects observed with NM-203. Here, we compare the effects of low doses of NM-200 and NM-203 on human macrophage-like THP-1 cells, assessing how the pre-exposure to these nanomaterials affects the cell response to lipopolysaccharide (LPS). Cell viability was affected by NM-203, but not by NM-200, and only in the presence of LPS. While NM-203 stimulated mTORC1, neither ASNPs activated NFκB or the transcription of its target genes PTGS2 and IL1B. NM-200 and NM-203 caused a block of the autophagic flux and inhibited the LPS-dependent increase of Glutamine Synthetase (GS) expression. Both ASNPs suppressed the activation of caspase-1, delaying the LPS-dependent secretion of IL-1β. Thus, ASNPs modulate several important pathways in human macrophages, altering their response to LPS. NM-203 had larger effects on autophagy, mTORC1 activity and GS expression than NM-200, confirming the higher biological activity of pyrogenic ASNPs when compared with precipitated ASNPs.