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GST-4-dependent suppression of neurodegeneration in C. elegans models of Parkinson’s and Machado-Joseph Disease by rapeseed pomace extract supplementation.

Pohl, Franziska; Teixeira-Castro, Andreia; Costa, Marta Daniela; Lindsay, Victoria; Fiúza-Fernandes, Juliana; Goua, Marie; Bermano, Giovanna; Russell, Wendy; Maciel, Patrícia; Kong Thoo Lin, Paul

Authors

Franziska Pohl

Andreia Teixeira-Castro

Marta Daniela Costa

Victoria Lindsay

Juliana Fiúza-Fernandes

Marie Goua

Giovanna Bermano

Wendy Russell

Patrícia Maciel

Paul Kong Thoo Lin



Abstract

Genetic mutations and aging-associated oxidative damage underlie the onset and progression of neurodegenerative diseases, like Parkinson’s disease (PD) and Machado-Joseph disease (MJD). Natural products derived from plants have been regarded as important sources of novel bioactive compounds to counteract neurodegeneration. Here, we tested the neuroprotective effect of an ethanolic extract of rapeseed pomace (RSP), a rapeseed (canola) oil production by-product, in C. elegans models of MJD and PD. The extract, containing sinapine and other phenolics, restored motor function of mutant ataxin-3 (ATXN3) animals (MJD) and prevented degeneration of dopaminergic neurons in one toxin-induced and two genetic models of PD. Whole-organism sensors of antioxidant and xenobiotic response activation revealed the induction of phase II detoxification enzymes, including glutathione S- transferase (GST-4) upon RSP extract supplementation. Furthermore in vivo pharmacogenetic studies confirmed gst-4 is required for the therapeutic effect of RSP extract in the two disease models. The results suggest that GST-4-mediated antioxidant pathways may constitute promising therapeutic co-targets for neurodegenerative diseases and confirm the utility of searching for bioactive compounds in novel sources, including food and agricultural waste/by-products, such as RSP.

Journal Article Type Article
Publication Date Dec 31, 2019
Journal Frontiers in Neuroscience
Print ISSN 1662-4548
Electronic ISSN 1662-453X
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 13
Article Number 1091
Institution Citation POHL, F., TEIXEIRA-CASTRO, A., COSTA, M.D., LINDSAY, V., FIÚZA-FERNANDES, J., GOUA, M., BERMANO, G., RUSSELL, W., MACIEL, P. and KONG THOO LIN, P. 2019. GST-4-dependent suppression of neurodegeneration in C. elegans models of Parkinson’s and Machado-Joseph Disease by rapeseed pomace extract supplementation. Frontiers in neuroscience [online], 13, article ID 1091. Available from: https://doi.org/10.3389/fnins.2019.01091
DOI https://doi.org/10.3389/fnins.2019.01091
Keywords Rapeseed (canola) pomace; C. elegans; Parkinson’s disease; Machado-Joseph disease; Spinocerebellar ataxia 3; Antioxidant; GST-4; SOD-3

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