Oleuropein Aglycone, an Olive Polyphenol, Influences Alpha-Synuclein Aggregation and Exerts Neuroprotective Effects in Different Parkinson's Disease Models
Por:
Basellini MJ, Granadino-Roldán JM, Torres-Ortega PV, Simmini G, Rubio-Martinez J, Marín-del Barrio S, Cappelletti G, Cascante M and Cañuelo A
Publicada:
1 dic 2025
Ahead of Print:
1 jul 2025
Resumen:
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.
Filiaciones:
Basellini MJ:
Department of Biosciences, Università degli Studi di Milano, Milan, Italy
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
Granadino-Roldán JM:
Departamento de Química Física y Analítica, Universidad de Jaén, Campus "Las Lagunillas" s/n, 23071, Jaén, Spain
Torres-Ortega PV:
Departamento de Biología Experimental, Universidad de Jaén, Campus "Las Lagunillas" s/n, 23071, Jaén, Spain
Simmini G:
Department of Biosciences, Università degli Studi di Milano, Milan, Italy
Rubio-Martinez J:
Department of Materials Science and Physical Chemistry and Institut de Recerca en Quimica Teòrica I Computacional (IQTCUB), University of Barcelona (UB), 08028, Barcelona, Spain
Marín-del Barrio S:
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
CIBER of Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III (ISCIII), Madrid, Spain
Institute of Biomedicine of University of Barcelona (IBUB), University of Barcelona (UB), Barcelona, Spain
Cappelletti G:
Department of Biosciences, Università degli Studi di Milano, Milan, Italy
Cascante M:
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
CIBER of Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III (ISCIII), Madrid, Spain
Institute of Biomedicine of University of Barcelona (IBUB), University of Barcelona (UB), Barcelona, Spain
Cañuelo A:
Departamento de Biología Experimental, Universidad de Jaén, Campus "Las Lagunillas" s/n, 23071, Jaén, Spain
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