Researchers Reverse Parkinson's Symptoms in Animals
06.22.06, 12:00 AM ET
THURSDAY, June 22 (HealthDay News) -- Focusing on a protein that mysteriously
accumulates in the brains of people with Parkinson's disease, researchers
have discovered a biological pathway that might some day lead to better
treatments for the neurological condition.
Clumps of the protein, called alpha-synuclein, "are hallmarks of Parkinson's
disease," said Aaron Gitler, a postdoctoral researcher in the laboratory of
Susan Lindquist at the Whitehead Institute in Cambridge, Mass. So, Gitlin and
a fellow postdoctoral researcher, Anil Cashikar, set out to determine whether
preventing formation of those clumps might prevent the death of neurons, the
brain cells whose deterioration causes the symptoms of Parkinson's.
They started with the simplest of organisms -- yeast cells -- using an array
engineered by the Harvard Institute of Proteonomics. The researchers infected
those cells with alpha-synuclein. They reasoned that if they identified genes
whose over-expression rescued a cell, that would tell them something about
how alpha-synuclein sickened a cell in the first place.
Most of the genes they identified were involved in the production and folding
of cellular proteins into the proper shape and the fine-tuning of those
proteins. Then, working with researchers at the University of Missouri,
Kansas City, they showed that a mutated form of alpha-synuclein destroyed a
key protein in this process, causing the cells to die.
The next step was to find a gene that increased production of this key
transport protein, to see if that would save the cells.
"We were surprised that when we tested this gene in higher animals -- fruit
flies, worms, rat cells -- remarkably we could reverse Parkinson's symptoms
in higher animals," Gitler said. "There are obvious implications for drug
targets and the basic mechanism of how the disease occurs."
The scientists tried several ways of increasing production of the transport
protein. In every case, the nerve cells were restored to health, Gitler said.
The study findings appear in the June 23 issue of the journal Science.
"The long-term goal is to find a drug target," said Cole M. Haynes, who took
part in the research at the University of Missouri and now is a postdoctoral
fellow at New York University School of Medicine. "These proteins are the
possible target," he said.
The progress made thus far is just a beginning, Gitler added. "We hope that in
the long run we can get a very good understanding of this and other cellular
defects," he said. "Knowing these details will allow us and others to design
therapies for Parkinson's disease and other disease."
In a statement, Lindquist said, "We hoped that we could use these simple model
organisms to study something as deeply complex as neurodegenerative disease.
Most people thought we were crazy. But we now not only have made progress in
understanding this dreadful disease, but we have a new platform for screening
pharmaceuticals."
Dr. Michael S. Okun, medical director of the National Parkinson Foundation and
co-director of the University of Florida's Movement Disorders Center, said
the new study provides "potentially important information for researchers
interested in the neurodegenerative process that leads to Parkinson's
disease.
"The information from this study will be potentially useful to investigators
around the world interested in why brain cells die in Parkinson's disease,
and the results will hopefully be applied to more complex research model
systems," Okun said.
Parkinson's disease is a brain disorder that occurs when certain nerve cells
in the brain die or become impaired. Symptoms can include tremors, slowness
of movement, stiffness, trouble with balance, muffled speech and depression.
An estimated 1.5 million Americans have the disease, with 60,000 new cases
diagnosed annually. The condition typically develops after age 65, according
to the National Parkinson Foundation.
More information
The full facts about Parkinson's disease are available from the National
Library of Medicine.

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