CU finds how gene may help in Parkinson's fight

Analysis might spur new drugs to battle degenerative disease

Bill Scanlon, Rocky Mountain News

Published December 29, 2005 at midnight

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Colorado researchers have uncovered how a gene linked to Parkinson's disease can keep brain cells alive.

The discovery could lead to new drugs to spur the gene into acting properly and stopping Parkinson's disease at its earliest stages.

Researchers at the University of Colorado at Denver and Health Sciences Center performed a detailed analysis of the gene DJ-1. They found that when DJ-1 is functioning properly, it can prevent dopamine cells in the brain from dying.

When DJ-1 is abnormal, it can lead to nerve degeneration.

Parkinson's disease occurs when dopamine cells in the brain die or are damaged.

That makes it difficult for the brain to transmit messages to the body to make movements. Boxing legend Muhammad Ali and actor Michael J. Fox are among the celebrities who have the disease.

CU researchers found that when the DJ-1 gene was over-expressed - that is, more copies than normal - in dopamine cells, the cells were protected from different kinds of chemical stress. That demonstrated that the gene plays an important role in keeping dopamine cells healthy.

When there is an ample supply of DJ-1, the gene can spur the making of a helpful antioxidant to combat oxidant stress, or turn on the production of a protein that helps clean up abnormal proteins.

"Our research shows how a genetic cause of Parkinson's disease works," said Dr. Curt Freed, division head of clinical pharmacology and toxicology at the CU School of Medicine. He is co-author of the study that will appear in Friday's issue of the Journal of Biological Chemistry.

"We show how the normal function of the gene keeps dopamine cells from dying," Freed said. "If the gene is abnormal, these protective mechanisms cannot be brought into play."

DJ-1 is the third gene that has been linked to Parkinson's disease. Eleven different mutations have been found in the gene - suggesting that loss of DJ-1 function leads to neurodegeneration, said Wenbo Zhou, assistant professor of clinical pharmacology and toxicology at the CU School of Medicine, who was the lead investigator of the study.

CU scientists are involved in the search for new drugs to work with DJ-1 and fight Parkinson's.

"If we can find drugs that increase activity of the DJ-1 gene, we may be able to stop the relentless progression of Parkinson's disease even in patients who don't have mutations in the gene," Freed said. "Stopping a disease in its earliest stages would be a tremendous breakthrough."

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