At work. Nurr1, shown in white in the brain of embryonic mice, invites the development of nerve cells of the midbrain dopamine.
People with too little dopamine in their brains develop the debilitating symptoms of Parkinson's disease. Now scientists have identified a molecule that helps the brain get just the right amount of this neurotransmitter. The discovery, published in today's issue of Science * raises the possibility enticing that increasing or restoring the activity of this molecule, called Nurr1, omitting nerve cells could relieve or prevent Parkinson's disease.
researchers already knew that a gene called Nurr1 is most active in brain cells that produce dopamine. To find out what the gene's protein fact, a team led by Thomas Perlmann of the Ludwig Institute for Cancer Research and Lars Olson of the Karolinska Institute, both in Stockholm, Sweden, has created a strain of mice lacking the Nurr1 gene. These mice failed to nurse and died one day after birth. The only physical difference that the group could detect between KO and normal animals of the same age was in the midbrain region, which contains neurons that degenerate in Parkinson's disease. The cells were poorly organized, suggesting that they had never specialized in dopamine-producing neurons.
The team confirmed this suspicion by testing the presence of proteins known to be produced by these particular neurons. Nurr1, tyrosine hydroxylase (an enzyme essential for the production of dopamine) and of other proteins were all absent. Other experiments have suggested that Nurr1 not only causes dopamine cells to form in the first place, but it also helps produce the right amounts of dopamine. "Finding [protein] that affects such a specific [section] brain is very exciting," said neurobiologist Ron McKay of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. The results raise the tantalizing possibility that the increase or the restoration of Nurr1 activity in failing nerve cells can delay or prevent Parkinson's symptoms.
It may also help researchers track down the cause of the disease. Because Parkinson's disease does not seem to run in families, experts have long sought an external cause, such as a toxic environment. It may now be possible to narrow the search by looking at how the potential toxic substances affect Nurr1. And that could lead to treatment, says molecular biologist Orla Conneely Baylor College of Medicine in Houston, whose team discovered the origin Nurr1: "If we find [toxicants] that inhibit the activity of Nurr1, we can then be able to identify drugs that can counteract that. "
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