Shooting the messenger: Glutamate targeted with new research funds

On the path from the eye to the brain, visual information travels between neurons via glutamate. Glutamate levels are crucial to cell communication: too high and neurons die, too low and information cannot be properly understood. In either case, the wrong balance of glutamate in the neurons can contribute to neurological diseases including stroke, glaucoma, and Alzheimer's.

A new research team led by Dr. Don van Meyel, Director of the Centre for Translational Biology of the Research Institute of the McGill University Health Centre (RI-MUHC), has been awarded close to $1.5 million to develop a glutamate biosensor platform for brain diseases. The researchers, including Dr. Tim Murphy at the Djavad Mowafaghian Centre for Brain Health, will exploit an innovative protein engineering technology called Cyto-iGluSnFR, allowing them to detect the glutamate levels that enter cells in the brain and retina.

“These tools will enable us to get a new look at glutamate, a major neurotransmitter,” says Dr. Murphy. “Until now, glutamate has not been a drug target; it was thought to be too central to brain function and too ubiquitous to target. Now with these new tools, specifically Cyto-iGluSnFR, we have a selective target.”

This research project, along with five others across Canada, was awarded funding by the CQDM, Brain Canada and the Ontario Brain Institute (OBI) to address unmet needs in neuroscience within their Focus on Brain strategic initiative. This total funding announcement of $10 million was made recently at the annual meeting of the Canadian Association for Neuroscience being held in Vancouver.

Glutamate levels in the brain are precisely regulated by glial cells that are located near neurons, through transport proteins on their surface called excitatory amino acid transporters (EAATs). EAATs are very attractive targets for the development of new drug therapies.

"This funding will allow us to adapt Cyto-iGluSnFR technology for targeting EAAT function and permit the screening of millions of chemical compounds in search of those that modulate these proteins," explains Dr. Murai, neuroscientist and associate professor in the Department of Neurology and Neurosurgery at McGill University. "These compounds could lead to the development of drugs allowing the modulation and restoration of glutamate flow into glial cells of the brain and retina."

For more information on Brain Canada funding and initiatives, visit braincanada.ca.