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