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Byproducts of canola oil production show therapeutic potential for MJD and Parkinson’s Disease

Written by Dr. Maria do Carmo Costa, Edited by Dr. Hayley McLoughlin

Collaboration between researchers in Portugal and the United Kingdom discover that a canola oil by-product shows promise, corrects MJD/SCA3 and Parkinson’s Disease symptoms in animal models.

Isolated compounds or extracts (containing a mixture of compounds) from certain plants are showing promise as potential anti-aging drugs or as therapeutics for neurodegenerative diseases. Some of these plant compounds or extracts can improve the capacity of cells to fight oxidative stress that is defective in aging and in some neurodegenerative diseases. Machado-Joseph disease, also known as Spinocerebellar ataxia type 3, and Parkinson’s disease are two neurodegenerative diseases in which cells inability to defend against oxidative stress contributes to neuronal death. In this study, the groups of Dr. Thoo Lin and Dr. Maciel partnered to test the therapeutic potential of an extract from the canola plant rapeseed pomace (RSP) with antioxidant properties in Machado-Joseph disease and Parkinson’s disease worm (Caenorhabditis elegans) models.

Canola field with snowcapped mountains in the background, image courtesy of USDA NRCS Montana on Flickr.

Machado-Joseph disease is a dominant neurodegenerative ataxia caused by an expansion of CAG nucleotides in the ATXN3 gene resulting in a mutant protein (ATXN3). While in unaffected individuals this CAG repeat harbors 12 to 51 trinucleotides, in patients with Machado-Joseph disease contains 55 to 88 CAG repeats. As each CAG trinucleotide in the ATXN3 gene encodes one amino acid glutamine (Q), the disease protein harbors a stretch of continuous Qs, also known as polyglutamine (polyQ) tract.

Parkinson’s disease that is characterized by loss of dopaminergic neurons can be caused either by genetic mutations or by environmental factors. Mutations in the genes encoding the protein a-synuclein and the enzyme tyrosine hydroxylase (a crucial enzyme for the production of dopamine) are amongst the genetic causes of patients with Parkinson’s disease.

In this study Pohl, Teixeira-Castro and collaborators used Machado-Joseph disease worms genetically modified to produce in their neurons human mutant ATXN3 protein. In these worms, the mutant protein aggregates in neurons and causes motility defects in worms, replicating aspects of the human Machado-Joseph disease. The investigators also used worms that were genetically modified in the same way but overexpressing normal human ATXN3 protein found in individuals unaffected with Machado-Joseph disease – these worms show normal movement and the normal protein does not aggregate in neurons reproducing the natural human condition.

On another hand, the authors used several worm models that show loss of dopaminergic neurons resembling Parkinson’s disease caused by either genetic or environmental factors. They used worms that were genetically modified to produce human a-synuclein proteins or to overexpress tyrosine hydroxylase, or worms treated with a chemical that kills dopaminergic neurons.

Importantly, the authors show in this study that the treatment of Machado-Joseph disease or Parkinson’s disease worms with RPS, a byproduct of canola oil production, decreases signs of these diseases. Briefly, mutant Machado-Joseph disease worms treated with RPS showed restored movement to levels found in unaffected animals, and Parkinson’s disease worms treated with RPS showed preservation of dopaminergic neurons.

Next, the investigators showed that the RPS treatment rescued disease signs in Machado-Joseph disease and Parkinson’s disease worms by activating pathways that protect against oxidative stress. Specifically, the authors found evidence of one particular protective pathway, known as glutathione S-transferase 4 (GST-4)-dependent cellular anti-oxidant response that is activated in Machado-Joseph disease and Parkinson’s disease worms treated with RPS.

While further studies need to be conducted to fully understand how RPS extract rescues signs of Machado-Joseph disease and Parkinson’s disease particularly in vertebrate animals, the enzyme GST-4 seems to be a good therapeutic target for these diseases. Overall, this study demonstrates that boosting particular defenses against oxidative stress is a potential route for therapy in Machado-Joseph disease and Parkinson’s disease.

Key Terms

CAG repeat: A stretch of DNA that was the sequence CAG repeated many times. Everyone has repeating CAG tracts in some genes, but once they are over a certain length they can lead to disease, like Machado-Joseph disease.

Caenorhabditis elegans: A type of very small worm-like animals called nematodes. C. elegans are very simple organisms, but can be used to learn about more diseases in more complex organisms like humans. To learn more, check out our Snapshot on C. elegans.

Dopaminergic neurons: A type of neuron found in the nervous system that make dopamine. Although they make up less than 5% of all the neurons in the body, they play important roles in the movement, mood, and stress.

Oxidative stress: A type of disturbance in the normal functioning of a cell caused by an imbalance in the levels of reactive oxygen species. These oxygen species are produced as a normal byproduct of cellular metabolism and are usually cleared by the cell without much trouble. When cells are unable to sufficiently clear reactive oxygen species, these molecules begin to accumulate and cause damage to components that form a cell’s critical structures, such as lipids, proteins, and DNA. As we age, our cells naturally become less efficient at clearing reactive oxygen species and the level of oxidative stress we experience increases.

Conflict of Interest Statement

The authors and editor declare no conflict of interest.

Two of the authors on the original paper (P. Maciel and F. Pohl) are contributors to SCAsource. Neither of these authors had any contribution to the writing or editing of this summary.

Citation of Article Reviewed

Pohl F, Teixeira-Castro A, Costa M, Lindsay V, Fiúza-Fernandes J, Goua M, Bermano G, Russell W, Maciel P, Kong Thoo Lin P. 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. 2019;13:1091. doi: 10.3389/fnins.2019.01091

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