Researchers discover how a gene linked to Parkinson’s disease can keep brain cells alive

Dec 29 2005

Researchers at the University of Colorado at Denver and Health Sciences Center’s School of Medicine have uncovered how a gene linked to Parkinson’s disease can keep brain cells alive. The results suggest the possibility for new drugs that might regulate the gene and protect Parkinson’s patients from further cell damage. The findings will be published in the Dec. 30 issue of the Journal of Biological Chemistry.

Parkinson’s disease is a disorder that occurs when dopamine cells in the brain die or are damaged, making it increasingly difficult to relay movement messages from the brain to the body. CU School of Medicine scientists performed a detailed analysis of a gene known to be linked to Parkinson’s disease called DJ-1. The research showed that DJ-1, when functioning properly, can prevent dopamine cell death in the brain. If the DJ-1 gene is abnormal and doesn’t function properly, it can lead to the onset of neurodegeneration, particularly Parkinson’s disease.

CU School of Medicine researchers found that over-expressing the gene in dopamine cells can protect the cells from different kinds of chemical stress, showing that the gene plays a pivotal role in keeping dopamine cells healthy. The authors point out that if the cells are subjected to oxidative stress, then the DJ-1 gene turns on the production of the antioxidant peptide, glutathione. When acting in this way, the DJ-1 protein can also modify itself and absorb the damage caused by oxidative stress, thus protecting other important cellular function in the process. On the other hand, if damaged proteins are accumulating and harming the cells, then DJ-1 turns on the production of a different protein called Hsp70 to help clean up the abnormal proteins.

“Our research shows how a genetic cause of Parkinson’s disease works,” said Curt Freed, MD, professor and division head of clinical pharmacology and toxicology at the CU School of Medicine and co-author of the study. “We show how the normal function of the gene keeps dopamine cells from dying. 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 with recessive inheritance have been found in the gene and the gene has been linked to Parkinson’s disease – suggesting that loss of DJ-1 function leads to neurodegeneration,” said Wenbo Zhou, PhD, assistant professor of clinical pharmacology and toxicology at the CU School of Medicine and lead investigator of the study.

The results of the study have spurred a search for new drugs by the CU scientists involved in the research. “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,” Dr. Freed said. “Stopping a disease in its earliest stages would be a tremendous breakthrough.”

The CU School of Medicine faculty work to advance science and improve care as the physicians, educators and scientists at the University of Colorado Hospital, The Children’s Hospital, Denver Health Medical Center, National Jewish Medical and Research Center, and the Veterans Administration Medical Center. The School is part of the University of Colorado at Denver and Health Sciences Center, one of three campuses in the University of Colorado system.

http://www.uchsc.edu/sm/sm/