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LATEST VA RESEARCH ON PARKINSON'S DISEASE --
Finds brain
protein pathway may be a key to Parkinson's
disease.
Story here...
http://media-newswire.com/release_1040368.html
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Brain protein pathway may be a key to Parkinson's disease
A protein called HIPK2 is essential for the
survival of dopamine neurons, the cells lost in Parkinson’s disease,
according to a study in mice. The results suggest that the molecular
pathway in which the protein functions could be a possible new target
for therapy, the study authors say.
(Media-Newswire.com) - Parkinson’s disease is a degenerative disorder of
the central nervous system in which dopamine neurons die. Normally,
these cells produce the neurotransmitter dopamine, which transmits
signals along brain pathways to allow smooth, coordinated function of
the body's muscles and movement. The loss of the cells leads to
progressive impairment in motor skills and speech.
Scientists have speculated that HIPK2 might play a role in the survival
of dopamine neurons, says principal investigator Eric J. Huang, MD, PhD,
a staff physician at the San Francisco VA Medical Center, “but this is
the first demonstration in a living organism that knocking out HIPK2
leads to the death of these cells.”
The study appears in the January 2007 issue of Nature Neuroscience. It
was carried out using genetically engineered mice, developed in Huang’s
lab, that lack the gene for HIPK2, which is a transcription factor –– a
protein that regulates the expression of genes.
In the study, the team demonstrated that lack of HIPK2 causes the
absence of TGFbeta3, a neurotrophin –– a protein that promotes the
survival of brain and nerve cells. Lack of TGFbeta3 in turn leads to the
death of dopamine neurons, resulting in mice that are born with
Parkinson’s-like movement impairments.
Scientists do not know why dopamine neurons die in Parkinson’s disease,
but the current finding suggests that TGFbeta3 deficiency may be a key,
says Huang, who is also an associate professor of pathology at the
University of California, San Francisco.
In the study, Huang and his research team compared the brains of the
genetically engineered mice with those of normal, or wild-type, mice.
They found that among the genetically engineered mice, the midbrains,
where dopamine neurons are usually concentrated, had 40 to 50 percent
fewer dopamine neurons.
“Our results support the model that HIPK2 and TGFbeta3 regulate the
survival of dopamine neurons,” concludes Huang. “Whether we can actually
manipulate this system to help Parkinson’s patients is unclear right
now, and there are ongoing experiments to address that issue.”
Currently, the standard medication for Parkinson’s disease is the amino
acid L-dopa, which is converted to dopamine in the brain. “It works to
some extent, but a lot of patients suffer from side effects such as
involuntary movement because of the uncontrolled release of the
dopamine,” Huang notes. In addition, patients may develop a tolerance
for the drug and require increasingly larger doses.
Huang and his research team are also using the mice as a model to test
the hypothesis that one cause of Parkinson’s disease might be exposure
to neurotoxins –– substances in the environment that are poisonous to
brain and nerve tissue. “We want to see if the HIPK2-TGFbeta3 pathway
has a protective effect on dopamine neurons, and if the lack of that
pathway makes those neurons more vulnerable to neurotoxin damage,” he
says.
Lead authors of the study are Jiasheng Zhang, PhD, and Vanee Pho, PhD,
of SFVAMC and UCSF; other collaborators include Stephen J. Bonasera, MD,
PhD, Jed Holzmann, BS, Joanna Hellmuth, BS, Patricia H. Janak, PhD, and
Laurence H. Tecott, PhD, of UCSF; and Amy T. Tang, BS, and Siuwah Tang,
BS, of SFVAMC and UCSF.
The research was supported by funds from the Veterans Health
Administration and by grants from the National Institute of Neurological
Disorders and Stroke, the UCSF Alzheimer’s Disease Research Center, the
National Parkinson’s Foundation, and the Michael J. Fox Foundation for
Parkinson’s Research that were administered by the Northern California
Institute for Research and Education.
NCIRE is the largest research institute associated with a VA medical
center. Its mission is to improve the health and well-being of veterans
and the general public by supporting a world-class biomedical research
program conducted by the UCSF faculty at SFVAMC.
SFVAMC has the largest medical research program in the national VA
system, with more than 200 research scientists, all of whom are faculty
members at UCSF.
UCSF is a leading university that advances health worldwide by
conducting advanced biomedical research, educating graduate students in
the life sciences and health professions, and providing complex patient
care.
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Larry Scott
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