By studying the effects of rotenone on rat neurons, they discovered that one of the targets of the pesticide was microtubules intracellular highways for transporting various chemicals such as dopamine to the brain area that controls body movement.

Normally the enzyme parkin would protect the neuron from rotenone's assault on microtubules, Feng said.

"When microtubules are broken down by rotenone, the disassociated protein building blocks, called tubulin, are left behind," he said. "These tubulins are probably misfolded proteins. Left unattended, they could interfere with the normal assembly of microtubules. Based on our previous work that parkin marks this 'old' tubulin for rapid degradation, we theorize that parkin may thus prevent this interference."

Mutated parkin loses this protective ability, however, allowing rotenone to do its damage unchecked.

Feng and colleagues showed that rotenone damages the microtubules, which prevents dopamine from reaching the brain's movement center, causing a back-up in the dopamine transport system. Meanwhile, the backed-up dopamine accumulates in the neuron's cytoplasm and breaks down, causing a release of toxic free radicals, which destroy the neuron.

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Contact: Lois Bakjer
ljbaker@buffalo.edu
716-645-5000 x1417
University at Buffalo
3-Dec-2004