Overactive protein identified in Alzheimers

Scientists have identified a key player in the central nervous system, which when defective,contributes to many brain diseases, including Alzheimer’s. The discovery of the neurotransmitter glutamate opens up a vast field of potential therapy, according to the researchers at UC San Francisco.

Glutamate transmits critical instructions between nerve cells and carries out fundamental processes such as sensory perception, learning and memory. The release of too much glutamate causes excessive excitation in the nervous system. This in turn causes serious results such as the destruction of nerve cells associated with neurodegenerative diseases including Alzheimer’s disease.

“The discovery of the glutamate transporter represents a major missing component that people have sought for a long time,” says the senior author of the study, Robert H. Edwards, MD, UCSF professor of neurology and physiology. “It is one of the final things that will enable us to study the basic function of how synapses work.” Synapses are the place where a message, or nerve impulse, is passed from one brain cell to another.

Potential treatments could include a drug that blocks the release of excessive glutamate. “We’ve never had a drug that inhibits the release of glutamate, but we presume it would have dramatic effects,” says Edwards.

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 production of the protein-transporting gene. The resulting increase in this protein would enable nerve cells to store and release more glutamate.

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. Glutamate causes a high level of activity, nudging the brain into alert and enabling it to carry out the computations that underlie cognition and most other fundamental aspects of brain function.

The finding’s importance resembles that of the discovery of glutamate receptors, the proteins that respond to glutamate on target cells, says Edwards. “Our finding represents the flip side – the release of glutamate.”

The study was published in the August 11, 2000 issue of Science. The researchers will continue to investigate the characteristics of the glutamate protein and to try to determine how far-reaching its effects are on function.

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