Ruotolo Roberta, De Giorgio Giuseppe, Minato Ilaria, Bianchi Massimiliano G, Bussolati Ovidio, Marmiroli Nelson
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy.
Nanomaterials (Basel). 2020 Jan 29;10(2):235. doi: 10.3390/nano10020235.
Over the last decades, cerium oxide nanoparticles (CeO NPs) have gained great interest due to their potential applications, mainly in the fields of agriculture and biomedicine. Promising effects of CeO 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 CeO 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, CeO 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 CeO 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.
在过去几十年中，氧化铈纳米颗粒（CeO NPs）因其潜在应用而备受关注，主要应用于农业和生物医学领域。最近在一些神经退行性疾病中显示出CeO NPs的显著效果，但这些纳米颗粒在帕金森病（PD）中的作用机制仍有待研究。本研究通过使用基于人类α-突触核蛋白（α-syn）异源表达的酵母模型来解决这个问题，α-syn是路易小体的主要成分，而路易小体是PD的神经病理学标志。我们观察到CeO NPs以剂量依赖的方式强烈降低α-syn诱导的毒性。这种效应与抑制细胞质α-syn聚集灶的积累有关，导致NP处理后α-syn定位于质膜。此外，CeO NPs可抵消α-syn诱导的线粒体功能障碍，并减少酵母细胞中活性氧（ROS）的产生。使用细胞裂解物进行的体外结合试验表明，α-syn吸附在CeO NPs的表面，这表明这些纳米颗粒可能不仅作为自由基清除剂，而且通过在体内与α-syn直接相互作用，作为α-syn毒性的强抑制剂发挥作用。
