Pesticides and Parkinson Disease

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http://ehp.niehs.nih.gov/docs/2004/112-10/forum.html?section=environmental#pest<\

http://ehp.niehs.nih.gov/docs/2004/112-10/forum.html?section=environmental#pest>

Pesticides and Parkinson Disease<>

In support of the theory that the most common form of Parkinson disease (PD) may

result to some degree from exposure to environmental toxicants, researchers at

Emory University have identified a mechanism of toxicity linking the pesticide

rotenone to the same kind of cell damage that is associated with PD. Experiments

in both cell culture and rats demonstrated that the insecticide, derived from

natural compounds and often used in organic gardening and farming, reproduced

many of the pathological features of PD, including progressive damage to neurons

in the brain's basal ganglia that are vital to transmission of dopamine.

In the November 2003 Journal of Neuroscience, Emory researchers Tim Greenamyre

and Todd Sherer report that rotenone does its damage within the neuron's

mitochondria by inhibiting a crucial enzyme in the electron transport chain

known as complex I. Chronic treatment with low concentrations of rotenone

inhibited complex I, leading to oxidative stress and gradual degeneration of

dopamine neurons in rats, followed by a buildup of protein inside the nerve

cells like that known to occur in certain PD patients. The rats also

demonstrated an associated movement disorder.

The researchers then examined synthetic pesticides that are used in much greater

quantities than rotenone, and that are also known to disrupt complex I in

mitochondria. In findings reported at the November 2003 annual meeting of the

Society for Neuroscience, they found that pyridaben, used to control mites on

fruits and vegetables, was far more toxic than rotenone. " In a human

neuroblastoma cell culture, pyridaben did the same thing as rotenone, but much

more potently, " says Greenamyre. Pyridaben has not yet been tested in vivo.

The researchers cannot yet say whether the new findings should prompt concern

about chronic exposure to these chemicals. But what the work does do is show

that the way these pesticides affect dopaminergic neurons mirrors what happens

when genes go awry. A handful of rare mutations associated with PD have been

discovered that appear to affect neurons in the same way, Greenamyre says: " The

diverse causes of Parkinson's disease may all be related mechanistically--that

is, by oxidative damage, protein mishandling, and mitochondrial impairment. "

According to University of Pittsburgh scientist Hastings, some

epidemiological data suggest that some people may be at increased risk due to

pesticide exposure. However, she says, it's much more likely that increased risk

arises through a combination of level and route of exposure and genetic

susceptibility.

J. Langston, founder of The Parkinson's Institute

http://www.parkinsonsinstitute.org<http://www.parkinsonsinstitute.org/> and one

of the field's pioneers, agrees. " A lot of people are likely exposed to these

pesticides, but few develop Parkinson's disease, so [this research] suggests

that those who do develop it have genetic predilections, " he says.

Finding common mechanisms between rare forms of the disease and environmental

chemical exposures may offer a bit of good news, Greenamyre says. " If you can

define a common pathway that leads to neurodegeneration in Parkinson's disease, "

he says, " it may be possible to design drugs that protect that pathway. "

Renée Twombly