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Chemical That Triggers Parkinson's Disease Discovered
ScienceDaily (Oct. 31, 2007) 
— Researchers at the Saint Louis University School of Medicine have discovered 
the key brain chemical that causes Parkinson's disease - a breakthrough 
finding that could pave the way for new, far more effective therapies to 
treat one of the most common and debilitating neurological disorders.

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.

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