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Article Publish Status: FREE
Abstract Title:

Cucurbitacin E has neuroprotective properties and autophagic modulating activities on dopaminergic neurons.

Abstract Source:

Oxid Med Cell Longev. 2014 ;2014:425496. Epub 2014 Dec 9. PMID: 25574337

Abstract Author(s):

Anne-Marie Arel-Dubeau, Fanny Longpré, Julie Bournival, Cindy Tremblay, Julie Demers-Lamarche, Pavlina Haskova, Everaldo Attard, Marc Germain, Maria-Grazia Martinoli

Article Affiliation:

Anne-Marie Arel-Dubeau

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 thelysosomal 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.

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Sayer Ji
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