image of researcher
Frederique Larroquette
PhD student
McGill University

Piecing together the Parkinson’s puzzle: Investigating the impact of alpha-synuclein fibrils on dopaminergic neurons’ activity

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image of researcher

Frédérique Larroquette
PhD student
McGill University

At McGill University, Frédérique Larroquette, a PhD student, is conducting basic research to determine why only the brain cells that produce dopamine are vulnerable to the stressors that produce Parkinson’s disease.

Larroquette is transforming stem cells into dopaminergic brain cells to study the three puzzle pieces known to play some role in the development of the disease: clumps of a protein called alpha-synuclein, dysfunctional mitochondria within cells, and the misfiring of neurons.

Researchers who have devoted their careers to finding the cause of Parkinson’s disease have, collectively, identified three major drivers of the death of dopamine-producing brain cells. They know clumps of a protein called alpha-synuclein damaged mitochondria—the organelles that produce energy in cells—and misfiring neurons that disrupt electrical signals are all culprits that contribute to Parkinson’s disease.

But scientists still don’t know how these three culprits are linked, and why dopamine-producing neurons are the only type of brain cells so vulnerable to these stressors.

“We have three pieces of the puzzle, and we’re trying to fit them together,” says Larroquette.

Larroquette, a biomedical engineer, has decided to study neuroscience as well, to dig into the cellular functions causing this puzzle. Using stem cells derived from humans, she is transforming them into dopamine-producing neurons in cultures to mimic the activity in the human brain.

By studying the genetic mutations known to cause Parkinson’s, including mitochondrial damage within the cells, the behaviour of alpha synuclein and defects in the electrical activity of these cells, Larroquette hopes to find answers to how all these things fit together to cause Parkinson’s.

“It would be incredible if I could find the link between all three, because that’s the million-dollar question,” Larroquette says.

“It is really important to identify where the whole cascade starts, so that we are able to stop it,” she adds.

If Larroquette can discover the initial defect or disrupted process that ends in Parkinson’s disease that finding could influence the design of new drugs or treatments, she says.

Ultimately, her goal is to marry her background in bioengineering with her research skills so that she can design new drugs and therapeutics.

Although Larroquette does not personally know anyone who has Parkinson’s, she considers herself fortunate to have attended a Parkinson’s SuperWalk last year, where she met and interacted with people who are affected.

Now, she’s doing her best for the people she met who are living with this disease.

“I’m hopeful—we are at a period of time where there are so many new and cool tools that are being developed especially with the stem cells because we now have a human model of the disease,” she says.

“Through the efforts of a lot of people studying this, I think we’re probably going to be able to put the puzzle back together at some point.”

Read about other researchers recently funded by the Parkinson Canada Research Program by visiting the research section of www.parkinson.ca.


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