A New Target for Stroke and Alzheimer's Drugs

Brain receptors pinpointed as a new drug target for stroke and Alzheimers disease

(RxWiki News) The discovery of key brain receptors gives researchers new ammunition in finding new and innovative ways to treat Alzheimer's disease and disability from stroke.

University of Buffalo scientists found that critical brain receptors work in a manner opposite of what what was previously believed, creating the possibility that the finding could lead to a new drug target.

"See a neurologist if you suspect a neurodegenerative disorder."

Gabriela K. Popescu, senior study author and an associate professor of biochemistry in the University of Buffalo's School of Medicine and Biomedical Sciences, said this marks the first time that this site in the brain has been shown to be useful as a drug target. If a drug that attaches itself to the site and locks together subunits of certain receptors could be found, it would be a huge advantage in fighting disability from stroke, Alzheimer's and other neurodegenerative diseases, she said.

The discovery was made while focusing on NMDA and AMPA brain receptors for the neurotransmitter glutamate. The receptors, made of four subunits which are organized into pairs called dimers, have critical roles in learning and memory.

Since both receptors were so similar in structure, it had been assumed that the functioned in a similar way. But during the course of the study, Popescu said that when the site where the two subunits came together within each pair was altered, it was discovered that the NMDA receptor works the opposite of the AMPA receptor.

Locking the AMPA subunits together led to more activity, while the opposite was true in NMDA receptors. In achieving a reduction in NMDA activity, the amount of calcium entering neurons in response to neurotransmitter glutamate was lowered. That calcium overload in overactive NMDA receptors is what kills neurons and leads to symptoms of stroke, Alzheimer's and other neurodegenerative diseases.

The finding could allow scientists to develop therapies that could reduce NMDA receptor activity to treat, or possibly someday prevent stroke or Alzheimer's disease. Such a discovery also could prompt creation of revamped drugs that inhibit only certain NMDA receptors, which could reduce side effects and allow for the possibility of medications with more specific effects.

The research was published Oct. 11 in Nature Communications.

Review Date: 
October 12, 2011