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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.
Adapted from materials provided by Saint Louis University.

Rayilyn Brown
Board Member AZNPF
Arizona Chapter National Parkinson's Foundation
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