Mitochondrial dysfunction and vulnerability to oxidative stress in induced dopaminergic neurons derived from idiopathic Parkinson’s disease patients
One of the keys to making progress in determining the causes of Parkinson’s is having the right investigational tools.
At the Université de Montreal, PhD candidate Emilie Legault, a neuroscientist, is excited about new technology she has to help her discover the role aging plays in non-familial, or idiopathic, forms of Parkinson’s.
“The main risk factor for this form of Parkinson’s is aging,” Legault says. “What we wanted to do is develop models to study the aging effect on neurons in these idiopathic cases.”
Previously, researchers using cellular models to study the death of dopamine-producing brain cells had to use rejuvenated or embryonic cells. Unlike most people who develop Parkinson’s, the cell models hadn’t aged.
Now, Legault can convert skin cells into brain cells while keeping the cells at the same age as their donors.
Using cells donated from people 60 to 90 who have Parkinson’s, she can investigate the effect aging has on those cells.
Legault will expose the neurons to toxins that can create a Parkinson-like environment for the cells.
Then she’ll compare the ability of the older brain cells to process stress and to clear away damaged mitochondria, the powerhouse portion of cells that generate energy.
A buildup of damaged mitochondria damages brain cells that produce dopamine, the central chemical responsible for movement. So too can oxidative stress: an imbalance between oxygen-containing molecules and stabilizing molecules in the body.
Legault will compare recycling and regulatory functions of cells from people with Parkinson’s with the abilities of cells donated by people without Parkinson’s.
If older neurons are less effective at recycling and regulating, that may be among the reasons people develop Parkinson’s as they age.
“Today, there is no drug that prevents the progression of the disease, and I think it’s because in the past we didn’t have the tools to study properly what would stop that progression,” Legault says.
She hopes to be able to classify the donor cells into two different groups – people who get Parkinson’s because they can’t clear damaged mitochondria, and those whose cells die because they can’t regulate stress, as well as to determine if different age groups have different causes.
Legault’s findings could open the door to different treatments depending on what is causing the Parkinson’s.
Legault, whose late grandmother had Parkinson’s, hopes her work will someday contribute to the development of personalized medicine.
“That would be the greatest outcome – for each and every patient, depending on their situation, their age, their condition, to have the proper medication that would be most effective for them and would stop the progression of Parkinson’s.”
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Legault, who is entering the second year of her PhD, intends to make her career in Parkinson’s research.
“This award helps me to develop my project as far as I can, and to evolve in this field of research in order to publish papers and get a good view of what can be done in the field,” she says.
Much of the research into the cause of Parkinson’s has been done by studying familial forms of the disease, Legault says, although only fewer than 10 per cent of people with Parkinson’s have a familial form.
That makes it vital that people donate to Parkinson Canada so the organization can fund research into what causes the non-familial, or sporadic forms of the illness, Legault says.
“We don’t know the cause for 90 per cent of Parkinson’s cases,” she says. “New models like the one we are using are just starting, so it’s really important to have the money to encourage researchers to use this method and try to understand more than just the cases of the disease that have been most studied.”
“We still don’t know what triggers Parkinson’s in most of the cases. There’s still a lot that is unknown that is needing to be studied and understood.”
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