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Disruption of nerve cell supply chain may contribute to Parkinson's
Date:5/12/2011

ndria are part of the railroad's cargo. They supply the energy that allows the axon to do its work.

For the study, O'Malley gave cultured mouse nerve cells a toxin called MPP+ that causes Parkinson's-like symptoms.

"MPP+ is a derivative of a synthetic form of heroin developed in California in the early 1980s," O'Malley says. "It came to scientists' attention when teenage abusers of the drug went to the hospital with Parkinson's disease symptoms."

O'Malley found that the toxin stopped the movement of mitochondria in the axon in 30 minutes. The railroad still functioned, shipping other cargo to the end of the axon. But most mitochondria either stopped moving or were headed for the cell body instead of the axon.

O'Malley suspected that this meant the mitochondria were damaged by the changes caused by the toxin and being shipped back to the cell body for repair. Additional tests supported this theory, showing that the mitochondria had lost their ability to maintain their membrane potential, a measure of mitochondrial fitness.

The specificity of this toxin for dopamine-producing cells is reinforced by the finding that other types of nerve cells did not have problems transporting mitochondria after toxin exposure. In a comparison between different nerve cell types, O'Malley found mitochondria in dopamine-producing nerve cells are smaller in size and travel three times slower. But she can't yet definitively say that these distinctions play a role in the problems caused by the toxin.

Scientists screened several compounds to see if they could block the toxin's effects. Only two antioxidants worked, glutathione and N-acetyl cysteine. The latter compound has already been shown to be effective in animal models of Parkinson's disease and is used as a treatment for other disorders in patients.

O'Malley is currently studying whether two genes linked to Parkinson's disease affect mitochondria damaged by the toxin.


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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

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