The loss of neurons from the substantia nigra region of the brain have been blamed for causing the symptoms of Parkinson's, which include uncontrollable tremors and difficulty moving arms and legs. Scientists have long suspected that the neurotransmitter dopamine, a protein called alpha-synuclein and calcium channels were somehow involved in destroying the neurons, but they had been unable to attribute neuron death to any single molecule.

Now for the first time, researchers from the Columbia University Medical Center have conducted studies showing that it is actually the three molecules acting together to kill neurons. "Though the interactions among the three molecules are complex, the flip side is that we now see that there are many options available to rescue the cells," says Eugene Mosharov, Ph.D., associate research scientist, who, along with David Sulzer, Ph.D., professor of neurology & psychiatry at Columbia University Medical Center, conducted the studies.

Specifically, the studies determined that neuron death is due to the calcium channels leading to an increase of dopamine inside the cell, causing the excess dopamine to react with the alpha-synuclein. This results in the formation of inactive complexes, which then "gum up" the ability of the cells to get rid of toxic waste. Over time, the waste builds up and eventually kill the cells. According to Drs. Mosharov and Sulzer, if just one of the three factors is missing, the neurons will survive. "It may be possible to save neurons and stop Parkinson's disease by interfering with just one of the three factors," Dr. Mosharov notes.

The study also found that the location of the dopamine inside the neurons determines its toxicity. Most of dopamine inside the neurons is packaged into compartments that are shipped to the cell's edge where the dopamine is released. The symptoms of Parkinson's come about when the amount of dopamine released by the cells falls. The researchers surmise that better treatments for the debilitating disease could come from pushing more dopamine into the compartments where it has no toxic effect on the cell. "That would be a magic treatment," says Dr. Mosharov. "Not only would it stop cells from dying and the disease from progressing, it would improve the patient's symptoms at the same time by giving their neurons more dopamine to release." While Drs. Mosharov and Sulzer are working on genetic therapies that could achieve this, they emphasize that any treatment ready for clinic trial is years away.

News Release: Parkinson's: Neurons destroyed by three simultaneous strikes  www.sciencedaily.com    April 29, 2009