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Scientists ID Compounds That Prevent Brain Nerve Damage

Finding could help develop new drugs to treat Alzheimer's, Parkinson's diseases

THURSDAY, Sept. 25, 2008 (HealthDay News) -- Duke University Medical Center scientists say they have found compounds that prevented brain injury and greatly improved survival in fruit flies with a Huntington's-like disease.

The compounds block the action of tissue transglutaminase (TGM2), an enzyme that may cause damage by forming strong bonds between proteins within cells.

"We were able to prevent Huntington's disease-like illness in mutant fruit flies by giving them orally active transglutaminase inhibitors," senior author Dr. Charles S. Greenberg, a professor of medicine and pathology at Duke University Medical Center, said in a Duke news release.

Huntington's disease, which is not curable, causes uncontrolled movement and mental deterioration later in life.

The findings were published in the Sept. 22 issue of Chemistry & Biology.

In addition to Huntington's, these compounds may hold promise for people with other polyglutamine diseases, Alzheimer's or Parkinson's diseases, according to study author Thung S. Lai, a Duke associate professor of medicine.

"Our findings may also help to develop drugs that block the pathology related to transglutaminase's action. That action has been linked to the development of tissue fibrosis, organ failure and aging," Lai said in the same news release. The scientists next plan to test whether these TGM2 inhibitors could prevent the fibrous tissue process that causes chronic renal, vascular and lung disease.

The most effective compounds used in the testing were a kinase inhibitor and a category of drugs that attack a sulfhydryl group in a protein. But while these compounds show promise, they are several years away from entering any human trials, Greenberg said.

More information

The National Institute of Neurological Disorders and Stroke has more about Huntington's disease.

SOURCE: Duke University, news release, Sept. 23, 2008
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