NEW GENETIC RESEARCH DEMONSTRATES POSSIBLE
CAUSE OF
INHERITED FORM OF
PARKINSON'S DISEASE
NEW YORK, NY (AUG. 26,
2004) - Columbia University Medical Center and Albert Einstein
College of Medicine researchers have identified a possible cause of an
inherited form of Parkinson's disease, which may be
related to more common forms of the disease. The findings are
reported in the August 27, 2004 issue of Science.
While the cause of most cases of Parkinson's disease is unknown, a few
cases are inherited and can be traced to mutations in four different
genes, including the alpha-synuclein gene. This is the first
study that may pinpoint the mechanism by which the mutant gene
initiates a cascade of events that causes this devastating neurological
disease.
"This discovery could aid in the development of new, targeted
treatments to slow or stop the disease progression," said David Sulzer,
Ph.D., professor of neurology and psychiatry at Columbia University
College of Physicians and Surgeons and senior author of the study.
"This is an extension of the genetic research that discovered the
mutant
alpha-synuclein gene and it is exciting to see how this information can
be used to possibly determine the cause of Parkinson's disease."
Blockage Causes Neuron
Death
Neurons that release dopamine, the neurotransmitter that controls
coordinated movement, slowly die in people with Parkinson's disease,
causing progressively more limited mobility and speech. Results
of the new research indicate that in patients with a mutant
alpha-synuclein gene, Parkinson's disease may be caused by a blockage
within dopamine neurons.
In the study, the mutant forms of alpha-synuclein protein was shown to
bind to protein disposal sites within dopamine neurons. This
creates a blockage that leads to the eventual death of the neurons.
The study was
conducted in dopamine neurons taken from mice.
Dr. Sulzer likens the situation to a garbage truck stalling at the
entrance to the town dump. "If the truck breaks down right in
front of the dump, not only does it fail to deliver its own garbage to
the dump, but it blocks all the other garbage trucks and the town fills
up with garbage," said Dr. Sulzer.
Together with Ana Maria Cuervo, M.D., Ph.D., assistant professor of
anatomy and structural biology at Albert Einstein College of Medicine
and the study's lead author, Dr. Sulzer is now using the study's
findings to examine whether a backup at the protein disposal sites also
plays a key role in the most common idiopathic form of Parkinson's,
which has no known cause.
"These patients do not carry a mutant alpha-synuclein gene, but their
alpha-synuclein proteins bear modifications not seen in healthy people
that may cause the protein to act as the mutant does," said Dr. Sulzer.
# # #
To contact Dr. Ana Maria Cuervo, please contact
Karen Gardner at Albert Einstein College of Medicine: (718) 430-3101; kgardner@aecom.yu.edu.
The research was supported by the National Institutes of Health, a
National Institute of Neurological Disorders and Stroke Udall Center
Grant, the Parkinson's Disease Foundation, the Lowenstein Foundation,
the Matheson foundation, the Huntington's Disease Society of American
and the Howard Hughes Medical Institute.
Leonidas Stefanis, M.D., Ph.D., assistant professor of neurology at
Columbia University Medical Center, and Harvard researchers Ross
Fredenburg and Peter T. Lansbury, Ph.D., associate professor of
neurology, also participated in the research.
*Located in New York City, Columbia University
Medical Center provides international leadership in basic and clinical
research, medical education, and health care. The medical center
includes the dedicated work of many physicians, scientists, and other
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scientists, who have achieved some of the 20th century's most
significant medical breakthroughs, continues today.
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