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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.01091

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

  • 1Robert Gordon University, United Kingdom
  • 2University of Minho, Portugal
  • 3University of Aberdeen, United Kingdom

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 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.

Keywords: rapeseed (canola) pomace, C. elegans, Parkinson’s disease (PD), Machado-Joseph disease (MJD), Spinocerebellar ataxia 3 (SCA3), antioxidant, gst-4, SOD-3, Neuroprotection

Received: 28 Jun 2019; Accepted: 27 Sep 2019.

Copyright: © 2019 Paul, Teixeira-Castro, Costa, Lindsay, Fiúza-Fernandes, Goua, Bermano, Russell, Maciel and Kong Thoo Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Paul Kong Thoo Lin, Robert Gordon University, Aberdeen, AB10 7QB, United Kingdom, p.v.s.kong-thoo-lin@rgu.ac.uk