In the dynamic world of the central nervous system, the neurotransmitter glutamate is a key player, ceaselessly transmitting critical instructions between nerve cells. Now, UCSF researchers have identified the protein that transports the chemical signal to its launch site in nerve cells, offering a possible new target for treating such diseases as Alzheimer's disease.

The discovery opens a vast field of potential therapy, for while glutamate carries out such fundamental processes as sensory perception, learning and memory, changes in its role contribute to many brain diseases. The release of too much glutamate causes excessive excitation in the nervous system that leads to seizures, contributes to injury after stroke, the perception of pain and even the destruction of nerve cells associated with neurodegeneratives diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (Lou Gehrig's disease). A drug that blocked the glutamate transporter from loading glutamate, thus reducing the release of glutamate, could treat these illnesses.

Alternatively, increasing the amount of glutamate released from certain nerve cells could improve learning, memory skills and overall cognitive function. In this case, therapy might simply involve taking a drug that increases the expression of the gene that produces the protein transporter. The resulting increased expression of the protein would enable nerve cells to store and release more glutamate.

"We've never had a drug that inhibits the release of glutamate, but we presume it would have dramatic effects," says the senior author of the study, Robert H. Edwards, MD, UCSF professor of neurology and physiology. Glutamate, like all neurotransmitters, is a chemical message released by one nerve cell and targeted at another. Thousands of glutamate molecules are released from a single cell, prompting a response in a neighboring cell, which prompts a response in yet another cell. The milli
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
10-Aug-2000