WINSTON-SALEM, N.C. – Using new technology to measure protein levels in human tissue, scientists at Wake Forest Baptist Medical Center hope to identify new targets for drugs to treat Alzheimer's disease and epilepsy. They reported their progress today in San Diego at the annual meeting of the Society for Neuroscience.
"Proteins are the real 'functional players' of genes," said Qiang Gu, Ph.D., an assistant professor of neurobiology and anatomy. "Being able to measure levels of a large number of proteins simultaneously is a step forward in understanding more about the disease process – and hopefully identifying new targets for drug treatment."
A project to map the human genome found that there are about 30,000 different genes. But little is known about the hundreds of thousands of proteins that are manufactured by genes. Genes exert their effects through these proteins. Humans and other organisms use the information in genes to "express" or manufacture proteins. A new science called proteomics is working to unravel when the proteins are made, how they interact with each other and what role they play in disease.
Using a new tool of proteomics, called antibody microarrays, Gu and colleagues are measuring levels of more than 500 different proteins in tissue samples. Their goal is to see if certain proteins are increased or decreased in patients with Alzheimer's disease and epilepsy – which would suggest new targets for medications.
For the epilepsy study, the researchers focused on patients whose seizures couldn't be controlled with medication who had surgery to remove a small portion of their temporal lobes, the part of the brain where the seizures originated. Tissue samples from two of these patients were compared with tissue samples from subjects of the same age and sex.
Testing revealed that proteins involved in signal transduction – or cell growth – were increased in the patients with epilepsy. The scientists identified a specific pathway within cells that uses these proteins.
"Our results suggest that an increase in signal transduction proteins may underlie the development of epilepsy," said Gu. "Drugs to inhibit this particular pathway could one day be a new treatment for epilepsy."
The researchers will continue the work by conducting animal studies to learn more about the pathway and when the proteins increase. "If the protein is increased in stages before the onset of epilepsy, perhaps there could be an intervention to prevent it," said Gu.
For the Alzheimer's study, the researchers compared brain tissue from four patients with the disease and four autopsy samples from people of the same age and sex. They identified a protein that was significantly higher in the brains of Alzheimer's patients.
Gu said finding a new treatment target for Alzheimer's disease would be especially important because there are no effective treatments for the disease and because of the disease's high prevalence.
"To find that levels of some proteins are decreased in Alzheimer's disease is not unusual, because of progressive nerve cell death associated with the disease," said Gu. "However, a significant increase of certain proteins in the brain indicates that they may play an important role in the disease process."
He said that for both diseases, there is likely to be more than one cause.
"Available evidence suggests that multiple factors may contribute to epilepsy and Alzheimer's disease," he said. "There are likely multiple pathways involved. Our goal was to identify proteins that could potentially be targeted by new drug treatments."
Tissue samples for the study were obtained from several sources, including the epilepsy program at Wake Forest Baptist, the Kathleen Price Bryan Brain Bank at Duke University Medical Center, and the National Disease Research Interchange Program.
Other researchers involved in the projects were Ali Al-Housseini, M.D., William Bell, M.D., Steven Glazier, M.D., Michael Tytell, Ph.D., and Kathy Widmer, M.Sc., all from Wake Forest Baptist.
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