UCD
researchers uncover the role of a gene linked to Parkinson’s Disease
Researchers at the University of Colorado Denver’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 were 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. 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.
The 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.”
