Duke team finds compounds that prevent nerve damage

Sep 23, 2008

Duke University Medical Center scientists have made a significant finding that could lead to better drugs for several degenerative diseases including Huntington's disease and Alzheimer's disease. Compounds that block the activity of a specific enzyme prevented brain injury and greatly improved survival in fruit flies that had the same disease process found in Huntington's disease.

"We were able to prevent Huntington's disease-like illness in mutant fruit flies by giving them orally active transglutaminase inhibitors," said Charles S. Greenberg, M.D., a Professor of Medicine and Pathology at Duke University Medical Center and senior author of the paper. The drug blocks the action of an enzyme called tissue transglutaminase (TGM2). TGM2 may damage cells by forming strong bonds between proteins. Such bonding is beneficial for blood clotting which happens outside of cells, but if this type of bonding occurs inside cells, it can be harmful, Greenberg said.

The study appears in the current issue of Chemistry and Biology.

Huntington's disease causes uncontrolled movement and mental deterioration that develops later in life, and though there is no cure, people can get tested to learn whether they have the gene that causes the devastating illness, Greenberg said.

Alzheimer's disease, Parkinson's disease and polyglutamine diseases including Huntington's disease may possibly be improved with the same compounds, said Thung S. Lai, Ph.D., lead author and 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."

While these compounds were promising in the animal system, they are several years away from entering any human trials, Greenberg said. "We will be studying these compounds in diseases in which TGM2 produces tissue injury."

For the study, Lai painstakingly screened 2,000 compounds. Only two groups of drugs were found to be effective TGM2 inhibitors. Some of the most potent TGM2 inhibitors were given to the fruit flies along with their food.

The most effective compound was a kinase inhibitor, a drug that had been developed several years ago for another purpose. The other beneficial compounds fell into a category of drugs that attack a sulfhydryl group in a protein.

The next step is to use the effective compounds as the backbone for developing even more effective drugs, Lai said. The scientists plan to test whether the TGM2 inhibitors they identified would prevent the fibrous tissue process that causes chronic renal, vascular and lung disease.

Source: Duke University Medical Center

Explore further: Connection found between birth size and brain disorders

add to favorites email to friend print save as pdf

Related Stories

Golden retriever study sniffs for cancer clues

34 minutes ago

(HealthDay)—Michael Court is a scientist and a dog lover, so he jumped at the chance to enroll his golden retriever in a nationwide study aimed at fighting cancer and other ills in canines.

Team makes scientific history with new cellular connection

53 minutes ago

Researchers led by Dr. Helen McNeill at the Lunenfeld-Tanenbaum Research Institute have revealed an exciting and unusual biochemical connection. Their discovery has implications for diseases linked to mitochondria, ...

First bill in Tesla deal sails through Assembly

57 minutes ago

The Nevada Assembly has unanimously approved the first of four bills that make up a package of up to $1.3 billion in tax breaks and incentives the Legislature is considering to seal a deal to bring Tesla ...

Study maps 15 years of carbon dioxide emissions on Earth

1 hour ago

World leaders face multiple barriers in their efforts to reach agreement on greenhouse gas emission policies. And, according to Arizona State University researchers, without globally consistent, independent ...

Recommended for you

Connection found between birth size and brain disorders

1 hour ago

(Medical Xpress)—A trio of researchers has found what appears to be a clear connection between birth size and weight, and the two brain disorders, autism and schizophrenia. In their paper published in Proceedings of ...

A novel therapy for sepsis?

19 hours ago

A University of Tokyo research group has discovered that pentatraxin 3 (PTX3), a protein that helps the innate immune system target invaders such as bacteria and viruses, can reduce mortality of mice suffering ...

User comments : 0