title: Cucurbitacin E has neuroprotective properties and autophagic modulating activities on dopaminergic neurons.
abstract: Natural molecules are under intensive study for their potential as preventive and/or adjuvant therapies for neurodegenerative disorders such as Parkinson's disease (PD). We evaluated the neuroprotective potential of cucurbitacin E (CuE), a tetracyclic triterpenoid phytosterol extracted from the Ecballium elaterium (Cucurbitaceae), using a known cellular model of PD, NGF-differentiated PC12. In our postmitotic experimental paradigm, neuronal cells were treated with the parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP(+)) to provoke significant cellular damage and apoptosis or with the potent N,N-diethyldithiocarbamate (DDC) to induce superoxide (O2(•-)) production, and CuE was administered prior to and during the neurotoxic treatment. We measured cellular death and reactive oxygen species to evaluate the antioxidant and antiapoptotic properties of CuE. In addition, we analyzed cellular macroautophagy, a bulk degradation process involving the lysosomal pathway. CuE showed neuroprotective effects on MPP(+)-induced cell death. However, CuE failed to rescue neuronal cells from oxidative stress induced by MPP(+) or DDC. Microscopy and western blot data show an intriguing involvement of CuE in maintaining lysosomal distribution and decreasing autophagy flux. Altogether, these data indicate that CuE decreases neuronal death and autophagic flux in a postmitotic cellular model of PD.
authors.affiliation: Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7.
authors.forename: Anne-Marie
authors.identifier: 0000-0001-9839-8245
authors.initials: AM
authors.lastname: Arel-Dubeau
authors.affiliation: Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7.
authors.forename: Fanny
authors.initials: F
authors.lastname: Longpré
authors.affiliation: Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7.
authors.forename: Julie
authors.initials: J
authors.lastname: Bournival
authors.affiliation: Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7.
authors.forename: Cindy
authors.initials: C
authors.lastname: Tremblay
authors.affiliation: Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7.
authors.forename: Julie
authors.identifier: 0000-0001-5838-6813
authors.initials: J
authors.lastname: Demers-Lamarche
authors.affiliation: Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7 ; Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, 500 50 Hradec Kralove, Czech Republic.
authors.forename: Pavlina
authors.initials: P
authors.lastname: Haskova
authors.affiliation: Institute of Earth Systems, University of Malta, Msida MSD 2080, Malta.
authors.forename: Everaldo
authors.initials: E
authors.lastname: Attard
authors.affiliation: Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7.
authors.forename: Marc
authors.identifier: 0000-0001-7942-3185
authors.initials: M
authors.lastname: Germain
authors.affiliation: Cellular Neurobiology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada G9A 5H7 ; Department of Psychiatry and Neuroscience, Laval University and CHU Research Center, Québec, QC, Canada G1W 1C2.
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Martinoli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014315:Triterpenes; C102326:cucurbitacin E