Research by neuroscientists at the University of Virginia Health System shows that oxygen free radicals are damaging proteins in mitochondria, the tiny cellular 'batteries' of brain cells. This damage may be one main cause of Parkinson's Disease (PD), the chronic movement disorder that affects at least one million Americans. UVa scientists believe the damage is taking place in a large protein structure called complex I, the first stop in the electron transport chain, which produces an electrical charge inside mitochondria. Mitochondria then use this electrical charge to make energy.
Using the brain cells from deceased Parkinson's patients who donated to the UVa brain bank, Dr. Jim Bennett, a UVa neurologist, and colleagues, isolated complex I from the mitochondria of ten Parkinson's brains and compared them to the complex I proteins from twelve normal brains. They discovered that the complex I assembly in Parkinson's had 50 percent more damage from oxygen. The complex I in Parkinson's brains also had evidence of not being properly assembled and had reduced electron flow, Bennett said.
"This part of the protein complex is being damaged by oxygen free radicals more in a brain with Parkinson's than it is in someone of same age who does not have PD," Bennett said. His research is published in the May 10th edition of the Journal of Neuroscience found on the web at www.jneurosci.org.
Oxygen free radicals are oxygen molecules that carry an extra electron. They are destructive because, in excessive amounts, they chemically attack the components of the cell, including proteins, DNA and lipids in cell membranes. One of the major problems of normal aging is an increased level of these free radical damaged proteins, along with damaged DNA and lipids.
Bennett believes that Parkinson's patients may benefit one day from drugs that can slow the damage from free radicals. "If we could soak up the free radicals in mitochondria, then complex I could repair itself," Bennett said. "If this damage is caught in people early on, we might interrupt the progression of Parkinson's disease. Such treatment is hypothetical at this point, but it is rational."
Right now, Bennett and his colleagues don't know why complex I was damaged in the Parkinson's patients. "It could be that something has gone terribly wrong with the mitrochondrial genome passed down by a person's mother that codes for several proteins in complex I," Bennett said. "Something could be wrong in the coding for genes that help complex I assemble. Or there could be environmental toxins. Our research is a first real step in understanding at a detailed biochemical level what the challenge is."
Bennett said he now plans to model the observation by extracting mitochondrial DNA from the cells of donated PD brains, put the DNA into a cell and express it to see if the phenomenon can be reproduced.
As part of a U.S. government effort to find the cause and a cure for PD, UVa is one of only 12 medical centers to be designated a Morris K. Udall Parkinson's Disease Center of Excellence by the National Institutes of Health. The NIH recently renewed a $1.3 million research grant to Bennett and his Udall team of investigators. Bennett's team is one of the few Udall Centers that does Parkinson's research on human brain cells.
Co-authors with Bennett on the paper in the Journal of Neuroscience are Paula M. Keeney, B.S., of the Center for the Study of Neurodegenerative Diseases at UVa, and Jing Xie, Ph.D., and Roderick Capaldi, Ph.D., both of the Institute of Molecular Biology at the University of Oregon.
J. Neurosci. 2006 26: 5256-5264; doi:10.1523/JNEUROSCI.0984-06.2006
Cite This Page: