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Protein connections: A network to understand disease

25,000 proteins, and they interact with one another. We know that many diseases are basically related back to mutations in genes. But what if the whole network was perturbed in a way to cause disease?"

"We picked 23 different disease genes to study," said Lim.

All of them caused the same kind of degeneration in nerve cells, even though they were different genes making different proteins.

"We felt they must have common protein partners," he said.

"We found that the proteins made by those 23 genes all interacted with one another," said Zoghbi. "They either interacted directly or indirectly through common partners. Proteins that we know can change the course of disease in animal models were also identified as common partners."

"In this network are spots where many proteins interact," she said. "These are key proteins."

These proteins, she said, could be extremely important in insuring normal neuronal function.

"When you step back, you realize this is applicable to any human disease," she said. "You start with a handful of genes you know cause disease and then go find their partners, and then their partners and then build a network that will include all the factors that make you susceptible to a disease or cause the symptoms of it."

"Instead of thinking one gene-one disease, you realize that if there are 10 genes that cause the same symptoms, they must do it through some common pathways or interactions with other proteins."

In applying the network theory to understanding disease, Zoghbi and her colleagues have come full circle. Symptoms used to always be the basis for medical treatment.

"Now we are providing a mechanistic basis for understanding why we treat symptoms," she said.

In the future, treatments may be designed to interrupt the cellular missteps that lead to disease.

Others who participated in this research include: Drs. Chad Shaw, Akash J. Patel and Joseph Fi

Source:Baylor College of Medicine

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