Over one million Americans suffer from Parkinson¿s disease, the cause of which is largely unknown. Although mutations in several proteins can lead to inherited forms of the disease, nobody knows what triggers the overwhelming number of sporadic cases. Now researchers from Emory University in Georgia have shown that the pesticide rotenone causes Parkinson¿s symptoms in rats by inhibiting an enzyme complex in the respiratory chain of their mitochondria.
Parkinson¿s normally starts late in life and leads to progressive muscle stiffness, tremors and slowness of movement. These symptoms arise because nerve cells producing the neurotransmitter dopamine, located in an area of the brain known as the substantia nigra, slowly die. Typically, fibrillar protein inclusions, so-called Lewy bodies, form in the cytoplasm.
In the December issue of Nature Neuroscience, the researchers report that when they continuously infused rats with low doses of rotenone, a plant-derived pesticide used as an insecticide and in fish control, the animals developed behavioral symptoms of Parkinson¿s. Also, their dopaminergic neurons died, and some contained inclusions similar to Lewy bodies. Rotenone easily crosses the cell membrane and inhibits the NADH dehydrogenase complex (complex I) in the respiratory chain of the mitochondria. Nevertheless, the researchers found that it does not significantly affect respiration in the brain. Instead it probably creates free radicals that cause oxidative damage, leading to protein inclusions and cell death. Dopaminergic nerve cells may in fact be especially sensitive to oxidative stress, which is why only they succumb.
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These results don't yet prove that Parkinson's disease in humans can result from long-term exposure to low levels of rotenone or similar pesticides. But epidemiological studies have identified pesticides as a risk factor for the disease. Thus, environmental substances that inhibit complex I of mitochondria may represent a major cause of Parkinson¿s.