Chemical That Triggers Parkinson's Disease Discovered

Currently, the main approach for treating Parkinson's disease, which afflicts more than 1.5 million Americans, is to replace dopamine that's lost when the cells that produce it die off and cause the disorder. With this new research, however, scientists can better work toward 'neuroprotective' therapies - those that actually block dopamine cells from dying off in the first place.

"We believe this work represents a very significant breakthrough in understanding the complicated chemical process that results in Parkinson's disease," said William J. Burke, M.D., Ph.D., professor of neurology at the Saint Louis University School of Medicine and the study's lead author.

"For the first time, we've identified the chemical that triggers the events in the brain that cause this disorder," Burke added. "We believe these findings can be used to develop therapies that can actually stop or slow this process."

Parkinson's disease occurs when some nerve cells in a part of the brain called the substantia nigra die or become impaired. Normally, these cells produce dopamine - a vital chemical that allows smooth, coordinated function of the body's muscles and movements.

When about 80 percent of these dopamine-producing cells die or are damaged, the symptoms of Parkinson's disease begin to appear. These include tremors and shaking, slowness of movement, rigidity and stiffness, and difficulty with balance.

Scientists have long known that a key protein called alpha-synuclein plays a role in the development of Parkinson's disease. Alpha-synuclein is found throughout the brain - but in some people, the protein clumps together. This causes the death of the dopamine-producing cells, which in turn causes Parkinson's to develop.

The SLU researchers discovered that dopamine itself actually plays a role in destroying the cells that produce it.

In the process that leads to Parkinson's disease, dopamine is converted into a highly toxic chemical called DOPAL. Using test-tube, cell-culture and animal models, the researchers found that it is DOPAL that causes alpha-synuclein protein in the brain to clump together, which in turn triggers the death of dopamine-producing cells and leads to Parkinson's.

"This is very exciting," Burke said. "This is the first time that anyone has ever established that it is a naturally occurring byproduct of dopamine that causes alpha-synuclein to aggregate, or clump together. It's actually DOPAL that kicks this whole process off and results in Parkinson's disease."

The research was supported by grants from the Missouri ADRDA Program, the Nestle Foundation, the St. Louis Veterans Administration Medical Center, the National Institutes of Health, the American Federation on Aging Research, the Alan A. and Edith L. Wolff Charitable Trust and the Blue Gator Foundation.

The scientists' findings are published in an early online edition of the journal Acta Neuropathologica.