Researchers in Montréal, led by Jacques Drouin, D.Sc., recently uncovered a mechanism regulating dopamine levels in the brain by working on a mouse model of late onset Parkinson’s disease. The study, conducted in collaboration with Dr. Rory A. Fisher from the department of pharmacology at the University of Iowa Carver College of Medicine, was published online by the scientific journal PLoS Genetics.
Using gene expression profiling, a method to measure the activity of thousands of genes, researchers investigated dopaminergic neurons in the midbrain, which are nerve cells that use dopamine to send signals to other nerve cells. These neurons are known to degenerate in Parkinson’s disease.
“The present work identified a cell signaling component, Rgs6, that is also restricted to the sensitive neurons in the midbrain and that exerts a protective function, particularly late in life,” explains Dr. Drouin, Director of the Molecular Genetics laboratory at the IRCM (Institut de recherches clinques de Montréal). “We had previously shown that this gene is itself controlled by a particular protein, known as PITX3, which plays an important role in the survival of these neurons.
“Through our study, we discovered that a defective Rgs6 gene causes the death of these neurons,” adds Dr. Drouin. “More specifically, we found that when we remove the Rgs6 gene, this relieves a brake against excessive dopaminergic signalling. As a result, excess free dopamine accumulation causes cellular stress, which, in turn, causes the neurons to die. While the loss of Rgs6 function may predispose or contribute to Parkinson’s disease, its stimulation may provide a
new target for the development of drugs against Parkinson’s disease.”
Drouin’s research was supported by the Canadian Institutes of Health Research (CIHR) and by Parkinson Society Canada. This latest discovery is built upon the results of an earlier pilot project to identify the genes targeted by PITX3, funded by Parkinson Society Canada’s National Research Program with a one year pilot project grant of $45,000.
Drouin got his first taste of the importance of research and what he calls “the beauty of proteins and what they do” when he was still in high school in Quebec City. He got a part-time job at a research lab at Laval University.
“That got me reading,” Drouin says. “That’s when I saw the first papers that described protein structure and linked them with their function. The fact that you could explain biology through the structure of proteins was quite startling to me.”
Drouin chose a research career in molecular genetics and biology because of his love for charting previously unknown scientific territory. He particularly enjoys discovering new structures in the brain, and the way different pathways work.
About Jacques Drouin, D.Sc.
Jacques Drouin obtained his Doctor of Science in Physiology from Université Laval. He is an IRCM Research Professor and Director of the Molecular Genetics research unit. Drouin is Research Professor in the Department of Biochemistry at the Université de Montréal. He is also associate member of the Department of Medicine (Division of Experimental Medicine), adjunct professor of the Department of Anatomy and Cell Biology, and adjunct member of the Department of Biochemistry at McGill University. In addition, he is an elected member of the Academy of Sciences of the Royal Society of Canada.