Pesticides and Parkinson disease.
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 Teresa 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 generic susceptibility.
J. William Langston, founder of The Parkinson's Institute 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."
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|Publication:||Environmental Health Perspectives|
|Date:||Jul 1, 2004|
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