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Unravelling the molecular mechanism of Parkin activation
Researchers now know that when a gene called Parkin is damaged, it can cause the familial form of Parkinson’s disease. Parkin’s role within brain cells is critical in making sure those cells produce energy and stay healthy.
What researchers need to know more about – and what biochemist Jacob Aguirre is investigating – is the chemical structure of Parkin. At the University of Western Ontario, Aguirre, a biochemist, uses a form of imaging called Nuclear Magnetic Resonance to study the structure of Parkin, right down to its foundation: Parkin’s atomic structure.
“Our hope is that if we can get a firm understanding of Parkin’s atomic structure, that this can provide clues into its function in the cell and why these mutations are causing dysfunction for this protein, resulting in disease,” Aguirre says.
Pinpointing the chemical description of Parkin would help other researchers design new drugs that could either stimulate or block the protein’s function in brain cells.
Most researchers believe Parkin’s role is positive – that it turns on a recycling function to rid cells of damaged mitochondria, the energy producers within all cells. Aguirre, a PhD student, is focused on finding a way to activate Parkin when it is mutated, to restore that positive recycling function.
“We’re hoping that we can use a rational drug design method to come up with small molecules or drugs that might activate this protein,” Aguirre says. “This is a much more targeted form of drug discovery, rather than just serendipitous drug discovery.”
For Aguirre, the search for a drug that could address the fundamental causes of Parkinson’s disease is personal. Alzheimer’s disease and Parkinson’s disease affected his great-grandfather and his grandmother. He knows too well the devastating effects of these progressively debilitating illnesses.
“When you are exposed to it at a young age, it makes you really want to try to get involved in the research,” Aguirre says.
He hopes his research into Parkin’s atomic structure could not only led to new drugs but might be applied to new techniques like gene therapy.
“This has a lot of potential,” Aguirre says.
The search for new drug targets can sometimes be a frustrating quest, but he is motivated by his genuine excitement about the work and the thrill of discovery.
“It’s really an exhilarating thing to find something new,” Aguirre says. “To be able to do that in a field that I’m also personally affected by is just the cherry on the top.”