Oleuropein Aglycone, an Olive Polyphenol, Influences Alpha-Synuclein Aggregation and Exerts Neuroprotective Effects in Different Parkinson's Disease Models
Alpha-synuclein aggregation is the pathological feature of several neurodegenerative disorders, including Parkinson's disease. The aggregates can diffuse within brain areas, and their toxicity has been proven in both cellular and animal models. Given that, recent therapeutic strategies have bee...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Fundació Sant Joan de Déu |
| Repositorio: | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| OAI Identifier: | oai:fsjd.fundanetsuite.com:p29375 |
| Acceso en línea: | https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29375 |
| Access Level: | acceso abierto |
| Palabra clave: | alpha-synuclein aggregation Parkinson's disease Synucleinopathy Oleuropein aglycone |
| Sumario: | Alpha-synuclein aggregation is the pathological feature of several neurodegenerative disorders, including Parkinson's disease. The aggregates can diffuse within brain areas, and their toxicity has been proven in both cellular and animal models. Given that, recent therapeutic strategies have been focusing on the identification of compounds able to promote the degradation of aggregates or, at least, to prevent the aggregation process. In this field, the use of natural-derived polyphenols has been proposed as a potential tool against alpha-synuclein pathology. On these bases, we tested the neuroprotective potential of oleuropein aglycone, an olive polyphenol, in two cellular and C. elegans-based models of Parkinson's disease. The compound was effective in reducing the burden of early-aggregates pathology upon alpha-synuclein overexpression in neuroblastoma cells, as well as neutralizing both the extent and the toxicity of administered preformed fibrils. In addition, oleuropein aglycone administration was beneficial for healthspan and lifespan in animals overexpressing alpha-synuclein, improved motor defects, recovered dopaminergic neuronal loss, and reduced the extent of alpha-synuclein pathology. Finally, through molecular modelling simulations, we propose a model for the alpha-synuclein and oleuropein aglycone interaction, predicting a dynamic that involves early alpha-synuclein oligomers. Overall, our results support the neuroprotective potential of oleuropein aglycone against alpha-synuclein aggregation and toxicity and shed light into the molecular features of these mechanisms, suggesting that further studies should be performed to gain insight about the neuroprotective actions of this polyphenol in humans. |
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