( In humans a dearth of the neurotransmi...)UCLA Find Yields Further Insight into Causes of Parkinson’s Diseas,Health

In humans, a dearth of the neurotransmitter dopamine has long been known to play a role in Parkinson's disease. It is also known that mutations in a protein called parkin// cause a form of Parkinson's that is inherited.

Now, UCLA scientists, reporting in the Jan. 31 issue of The Journal of Neuroscience, have put the two together. Using a new model of Parkinson's disease they developed in the simple Drosophila (fruit fly), the researchers show for the first time that a mutated form of the human parkin gene inserted into Drosophila specifically results in the death of dopaminergic cells, ultimately resulting in Parkinson's-like motor dysfunction in the fly. Thus, the interaction of mutant parkin with dopamine may be key to understanding the cause of familial Parkinson's disease — Parkinson's that runs in families.

Conventional wisdom has held that parkin is recessive, meaning that two copies of the mutated gene were required in order to see the clinical signs of Parkinson's disease. But the researchers, led by George Jackson, M.D., Ph.D., UCLA associate professor of neurology and senior scientist at the Semel Institute for Neuroscience and Human Behavior at UCLA, wanted to see if they could get the protein to act in a dominant fashion, so they put only one copy of the mutation into their fly model. The result was the death of the neurons that use dopamine, the neurotransmitter long implicated in Parkinson's disease.

"We put the mutant parkin in all different kinds of tissues and in different kinds of neurons, and it was toxic only to the ones that used dopamine," Jackson said. "No one's shown this degree of specificity for dopaminergic neurons."

Having a genetic model of Parkinson's disease (PD) in the fruit fly will allow researchers to run mass testing, or "screens," of genes in order to find the novel pathways — networks of interacting proteins that carry out biological functions — that control survival of those dopaminergic
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