Researchers in Montréal, Canada, led by Jacques Drouin (image), D.Sc., have 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 on December 11, 2014 in the open-access 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. “We identified the Rgs6 gene for its restricted expression in dopaminergic neurons,” explains Dr. Drouin, Director of the Molecular Genetics laboratory at the IRCM (Institut de Recherche Clinique de Montreal). “We had previously shown that this gene is itself controlled by a transcription factor called 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. Our work thus indicates that Rgs6 could be a new target for the development of drugs against Parkinson’s disease.”
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