Researchers discover new tool for investigating brain disorders, including dementia and depression

Graham Collingridge, senior investigator at Sinai Health’s Lunenfeld-Tanenbaum Research Institute and director of the Tanz Centre for Neurodegenerative Diseases at the University of Toronto, was part of an international consortium of researchers that created a new chemical tool for revealing how specific cell receptors function in the brain.

Their study, published recently in the journal Nature Communications, is an important step forward for studying Alzheimer’s, epilepsy, stroke and even Parkinson’s disease. The new compound targets certain members of the NMDA receptor, a class of receptor proteins that plays an essential role in learning and memory.

“Errors in NMDA receptors can lead to dementia and other serious disorders of the nervous system,” Collingridge explained. “Although we know that targeting NMDA receptors can be highly beneficial, there is room for improvement.”

Collingridge points to drugs like memantine, a medication used to delay memory loss in Alzheimer’s disease, and ketamine, an anesthetic and antidepressant. Both target NMDA receptors, but memantine offers only temporary relief and ketamine has potentially serious side effects.

Biologists from Cold Spring Harbor Laboratory in New York and chemists from the University of Bristol in the UK worked together to create chemical compounds that inhibit the activity of certain types of NMDA receptor.

The researchers hope by inhibiting some receptors while letting others function, they can now identify the roles different types of NMDA receptors play in both healthy and diseased brains.

“Both memantine and ketamine block all the subtypes with little selectivity,” Collingridge said. “Our new compounds just target two of the four major subtypes – the ones where we think the major therapeutic potential resides.”

Dr. Hiro Furukawa, principal investigator at Cold Spring Harbor Laboratory, co-led the study with Dr. David Jane’s chemistry lab at the University of Bristol. Moving forward, these two groups of collaborators will work on further refining the new compound for use in research.

Collingridge’s lab at LTRI in Toronto will focus on identifying which diseases it should target in developing new therapeutics  — including Alzheimer’s disease, Parkinson’s disease, depression and autism.