The reason why Parkinson's disease selectively harms brain cells which produce the chemical dopamine has been revealed by researchers at the Washington University School of Medicine.
Dopamine is involved in brain cell communications including the signals that control movement. As Parkinson's kills the dopamine-producing cells, patients begin to develop tremors, problem in moving and other symptoms.
The new study shows that a drug known to damage dopamine-producing nerve cells and mimic Parkinson's disease does so by rapidly damaging cellular energy generators called mitochondria.
"Much of the research into Parkinson's disease treatments is focused on saving the bodies of these cells, but our results suggest that keeping axons healthy also is essential," says Karen O'Malley of Washington University School of Medicine in St. Louis.
"When axons die back, dopamine is no longer delivered to the neurons that need it. The cell body also has fewer connections to other cells and it needs those connections to survive," she added.
She compared the axon's system for transporting supplies to a railroad. Mitochondria are part of the railroad's cargo. They supply the energy that allows the axon to do its work.
For the study, O'Malley gave cultured mouse nerve cells, a toxin called MPP+ that causes Parkinson's-like symptoms.
She found that the toxin stopped the movement of mitochondria in the axon in 30 minutes. The railroad still functioned, shipping other cargo to the end of the axon. But most mitochondria either stopped moving or were headed for the cell body instead of the axon.
Scientists screened several compounds to see if they could block the toxin's effects. They discovered that only two antioxidants, glutathione and N-acetyl cysteine worked.
N-acetyl cysteine has already been shown to be effective in animal models of Parkinson's disease and is used as a treatment for other disorders in patients.
The study has been published in The Journal of Neuroscience.