UB scientists find new target to treat neurological disease
LOIS BAKER
September 1, 2005(UB at Buffalo Reporter) - Neuroscientists from UB
have described for the first time how rotenone, an environmental
toxin linked specifically to Parkinson's disease, selectively
destroys the neurons that produce dopamine, the neurotransmitter
critical to body movement and muscle control.
Microtubules, intracellular highways that transport dopamine to the
brain area that controls body movement, are the crucial target, they
report.

Damage to microtubules prevents dopamine from reaching the brain's
movement center, causing a back-up of the neurotransmitter in the
transport system, the researchers found. The backed-up dopamine
accumulates in the body of the neuron and breaks down, causing a
release of toxic free radicals, which destroy the neuron.

The study appeared last month in the Journal of Biological Chemistry.

"This study shows how an environmental toxin affects the survival of
dopamine neurons by targeting microtubules that are critical for the
survival of dopamine-producing neurons," said Jian Feng, assistant
professor of physiology and biophysics in the School of Medicine and
Biomedical Sciences and senior author on the study.

"Based on these findings, we have identified several ways to
stabilize microtubules against the onslaught of rotenone. These
results ultimately may lead to novel therapies for Parkinson's
disease."

At least 500,000 people are believed to suffer from Parkinson's
disease in the United States, and about 50,000 new cases are reported
annually, according to the National Institutes of Health (NIH). These
figures are expected to increase as the population ages: The average
age of onset is about 60. The disorder appears to be slightly more
common in men than women.

Feng and colleagues in the Department of Physiology and Biophysics
have concentrated their research on the cellular mechanisms of the
disease. They are interested specifically in understanding why
rotenone destroys neurons that produce dopamine, while sparing
neurons that produce other neurotransmitters.

Using cultures of rat neurons, the researches subjected neurons that
produce various types of neurotransmitters to agents that mimic the
action of rotenone. These results showed that dopaminergic neurons
were destroyed while others survived.

They then topped off the treatment by adding the drug taxol, which
stabilizes microtubules and prevents their breakdown. Findings showed
that by protecting microtubules, the toxic effect of rotenone on
dopamine-producing neurons was greatly reduced.

"Based on these findings, we believe that microtubules are a critical
target of PD environmental toxins such as rotenone," said
Feng. "Since many microtubule-depolymerizing agents are compounds
naturally produced in many plants, our research points to the need to
examine their possible link to Parkinson's disease. In addition, PD
has a higher incidence in rural areas and is associated with
pesticides and insecticides frequently used in farming practices."

The research also opens up novel avenues for the development of PD
therapies by targeting microtubules, he said. Feng and colleagues in
his laboratory are working actively towards this goal.

Additional researchers on the study were Yong Ren, Wenhau Liu, Houbo
Jiang and Qian Jiang, postdoctoral associates in the Department of
Physiology and Biophysics.