title: Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE's ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.
authors: Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. imene.achour@uqtr.ca.
authors: Imène
authors: I
authors: Achour
authors: Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. anne-marie.arel-dubeau@uqtr.ca.
authors: Anne-Marie
authors: AM
authors: Arel-Dubeau
authors: Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. justine.renaud@uqtr.ca.
authors: Justine
authors: J
authors: Renaud
authors: Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. Manon.legrand@uqtr.ca.
authors: Manon
authors: M
authors: Legrand
authors: Institute of Earth Systems, University of Malta, Msida MSD 2080, Malta. everaldo.attard@um.edu.mt.
authors: Everaldo
authors: E
authors: Attard
authors: Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. Marc.Germain1@uqtr.ca.
authors: Marc
authors: M
authors: Germain
authors: Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. maria-grazia.martinoli@uqtr.ca.|Department of Psychiatry and Neuroscience, U. Laval and CHU Research Center, Québec, QC G9A 5H7, Canada. maria-grazia.martinoli@uqtr.ca.
authors: Maria-Grazia
authors: MG
authors: Martinoli
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D057888:Iridoid Glucosides; D039823:Iridoids; D017382:Reactive Oxygen Species; D013481:Superoxides; C002769:oleuropein; D016627:Oxidopamine
keywords: Parkinson’s disease; authophagy; cellular death; neurodegeneration; neuroprotection; oleuropein; oxidative stress; polyphenol