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SLU
scientists identify hemical that
triggers Parkinson’s Disease...New
research could yield therapies to slow or
stop the disorder
ST. LOUIS - 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.
Established in 1836, Saint Louis University School of
Medicine has the distinction of awarding the
first medical degree west of the Mississippi
River. The school educates physicians and
biomedical scientists, conducts medical
research, and provides health care on a
local, national and international level.
Research at the school seeks new cures and
treatments in five key areas: cancer, liver
disease, heart/lung disease, aging and brain
disease, and infectious disease.
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