Study holds promise for stroke, schizophrenia treatments

Researchers at the University of Toronto and the Centre for Addiction and Mental Health (CAMH) have discovered a communication link between proteins in the brain that could lead to improved treatments for psychiatric disorders and stroke.

The study, published in the Oct. 18 issue of the journal Cell, examined the interaction between two proteins known as dopamine D1 and NMDA receptors. The research group, led by Fang Liu, an assistant professor in U of T's Department of Psychiatry and CAMH's Section of Molecular Neurobiology, Neuroscience Research Department, found that two parts of the D1 receptor interact directly with two subunits of the NMDA receptor. These interactions modulate two separate NMDA functions in the brain - cell death and normal cell-to-cell communication. This study is the first to show that the interaction between D1 and the NMDA receptor also regulates - and, in fact, prevents - cell death.

"It may be possible to design a medication that specifically enhances this interaction leading to reduced cell death in the brain," says Liu. "This prevention of NMDA-mediated cell death could have important implications in terms of preventing brain damage in severe epilepsy, traumatic brain injury, neurodegenerative disorders and stroke."

Because cell death and cell-to-cell communication are regulated separately by the different D1 interactions, researchers may be able to manipulate one function without impacting the other, adds Liu. For example, it may be possible to design medication to enhance the interaction that regulates cell death, thereby preventing brain cells from dying, without inhibiting the other interaction regulating cell-to-cell communication. Cell death mediated by the NMDA receptor plays a critical role in the consequences and severity of stroke.

The discovery could also have significant impact on research into schizophrenia and other psychiatric disorders, creating the possibility that new antipsychotic med

Contact: Jessica Whiteside
University of Toronto

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