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Protein stimulates key link between nerve cells, suggesting possible target for mental retardation and nerve regeneration therapies

UCSF researchers have exposed a single protein that can stimulate the maturation of the synapses, or junctures, through which nerve cells communicate a key signal to one another. The discovery reveals a mechanism critical for supporting brain development, learning and memory and a possible target for treating mental retardation and nerve damage following stroke and spinal cord injury.

The finding, reported in the November 17 issue of Science, indicates that the protein, PSD-95, helps build the physical scaffolding of the synapse that cells use to transmit the chemical messenger, or neurotransmitter, known as glutamate, to a target cell. The protein also matures other aspects of the synapse -- enhancing the clustering of glutamate receptors on the target cells receiving the chemical messenger, increasing the number and size of the dendritic spines that hold glutamate receptors, and increasing the number of glutamate neurotransmitters emitted from the releasing cell.

The results, says senior author David S. Bredt, MD, PhD, UCSF professor of physiology, indicate that the protein is the cornerstone of physical maturation for both the pre- and post- synaptic structures that allow glutamate to signal from one neuron to another.

The findings are provocative, for glutamate, the major excitatory neurotransmitter in the brain, is the engine behind cellular learning -- including brain development and mental and physical processes. Glutamate is also thought to be the key to plasticity, the brain's ability to relearn mental and physical skills following injury and to adjust to new circumstances. The neurotransmitter acts by stimulating a receptor on target cells containing a protein known as the NMDA receptor, which serves to strengthen, or reinforce, the neural circuits between nerve cells that store memory.

Glutamate enables the brain to develop, language to be learned, a new math equation to be grasped, tennis to
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
16-Nov-2000


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