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St. Louis University scientists identify chemical that triggers Parkinson's disease
Date:10/30/2007

ST. LOUIS - Researchers at the Saint Louis University School of Medicine have discovered the key brain chemical that causes Parkinsons 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 Parkinsons disease, which afflicts more than 1.5 million Americans, is to replace dopamine thats 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 Parkinsons disease, said William J. Burke, M.D., Ph.D., professor of neurology at the Saint Louis University School of Medicine and the studys lead author.

For the first time, weve 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.

The scientists findings are published in an early online edition of the journal Acta Neuropathologica (http://www.springerlink.com/content/y875t47212001762/fulltext.html).

The researchers at Saint Louis University were joined in their effort by a team from Washington University in St. Louis.

Parkinsons 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 bodys muscles and movements.

When about 80 percent of these dopamine-producing cells die or are damaged, the symptoms of Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons.

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. Its actually DOPAL that kicks this whole process off and results in Parkinsons disease.


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Contact: Donn Walker
dwalke18@slu.edu
314-977-8015
Saint Louis University
Source:Eurekalert

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