Glutamate: The Other Brain Chemical

Dr. Philippe Huot
Assistant Professor
McGill University

Glutamate is the most abundant chemical in the brain, sending constant communication signals between nerve cells. Until recently, its role in Parkinson’s disease has been a mystery.

That’s because most researchers’ attention has been focused on dopamine, another signalling chemical, whose loss is responsible for the stiffness, tremor and shakiness people with this disease experience.

At McGill University, Dr. Philippe Huot, a neurologist and assistant professor, explores the relationship between both important brain chemicals. He’s searching for a way to control the release of glutamate.

“Everything is linked within the brain,” he says. “In Parkinson’s disease, there is a loss of dopamine, and less dopamine will cause abnormalities in glutamate-mediated signals. What we’re looking into is regulating that glutamate transmission.”

Using an experimental model of Parkinson’s disease, Huot and his team are testing the impact of some novel compounds, or potential new drugs, on metabotropic glutamate 2 (mGLU2) receptors in the brain. These receptors are the proteins that glutamates bind to within cells.

Too much glutamate has been implicated in the uncontrollable movements, called dyskinesia, that many people with Parkinson’s disease experience once they have been on levodopa. Levodopa is a synthetic form of dopamine, and is used to treat the motor symptoms people with Parkinson’s experience.

If Huot finds a compound that can block the release of glutamate, it could reduce people’s dyskinesia. Any drug developed out of this compound could also mean people would be able to take less dopamine, reducing its difficult side effects.

“What we find interesting is that this class of compounds appears to be able to alleviate more than one symptom of Parkinson’s disease,” Huot says. “That could also mean a reduction of the need to take multiple drugs.”

In addition to the time he spends in the lab looking for new treatment opportunities, Huot treats many people with Parkinson’s with the only medications that exist. He sees first-hand the impact of the current treatment, and that drives his research projects.

Originally, he says, his choice of a research career was motivated by both scientific curiosity about the causes of Parkinson’s and a desire to help people.

Now, he says the desire to make a difference in the lives of people with Parkinson’s keeps him moving forward.

“I see patients. The hope in their eyes — the questions that they ask about research — that’s what keeps me going in this field. I want to help them.”

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