Revealing the true face of a brain cell invader
Uncoupling pathology from neurotoxicity in synucleinopathies
After knowing people who were afflicted with neurodegenerative disorders while he was growing up, Maxime Rousseaux later encountered an even wider range of such patients through his university studies. Among his mentors was Dr. Michael Schlossmacher, whose Ottawa movement disorders clinic became an informal classroom where Rousseaux learned more about the human face of this condition.
“I met a lot of the individuals in the community and got really attached—not only emotionally invested but it felt like a sense of duty to work on the disease,” says Rousseaux, now a professor at the University of Ottawa. “That’s been with me for the past 12 years.”
This experience led him to focus on a particular brain protein called alpha-synuclein, which was first discovered decades ago and named for its localization at the synapses between brain cells and within the nucleus of those same cells.
This protein has also characterized as a contaminant that disrupts the function of brain cells and initiates the nervous system breakdown that defines Parkinson’s. Although that conclusion is supported by the substantial amounts of alpha-synuclein that are found in the areas of the brain where this breakdown is under way, Rousseaux notes that alpha-synuclein can also be found in cells in parts of the brain that remain unaffected. That finding leads the neuroscientist to wonder if the protein’s function is subtler than it appears to be.
“Is alpha-synuclein in the nucleus toxic, is it protective?” he asks. “We think it’s toxic in the nucleus and our work will test that hypothesis once and for all in the context of this pathology.”
This latest support from Parkinson Canada will make a crucial contribution to answering this question by enhancing the resources available to Rousseaux’s laboratory, he says. Other prospective sources of funding for such work would demand a great deal of preliminary data that he would not be able to obtain until his work is more advanced. With this funding, his research team now has a much greater ability to lay the foundation for better treatment of Parkinson’s patients.
“Our lab emulates specific genetic effects and tests their impact on cells, all in a search for the drivers of the molecular changes responsible for Parkinson’s,” he says. “The results will inform tailored therapies and promote drug development and pre-clinical testing.”