Mechanisms of rotenone action uncovered

Neuroscientists from the University at Buffalo have shown that rotenone, an environmental toxin linked specifically to Parkinson’s disease, damages dopamine producing neurons critical to body movement and muscle control.

The scientists report that microtubules, intracellular highways that transport dopamine to the brain area that controls body movement, are a crucial target for future therapies.

Damage to microtubules prevents dopamine from reaching the brain’s movement center, causing a back-up of the neurotransmitter in the transport system. 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 research suggests that rotenone targets microtubules and affects the survival of dopamine producing neurons whilst sparing neurons that produce neurotransmitters other than dopamine.

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 have identified several ways to stabilize microtubules against the onslaught of rotenone. These results ultimately may lead to novel therapies for Parkinson’s disease,” said Dr Jian Feng, assistant professor of physiology and biophysics in the University at Buffalo and senior author on the study.