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Nitric oxide links bulk of sporadic and familial Parkinson's disease

Johns Hopkins researchers have discovered that nitric oxide, a chemical messenger involved in bodily functions from erection to nerves' communication, also shuts down a protein involved in Parkinson's disease.

The finding finally provides a biochemical link between Parkinson's disease (PD) that occurs in families and the vast majority of cases which occur randomly in the population, as well as giving researchers a brand new target for developing treatments to slow or stop the disease.

The protein in question is parkin, and earlier research had shown that mutations that cripple it occur in about a third of patients with familial PD, but rarely show up in the much more common sporadic cases of the disorder. In the absence of these mutations, however, scientists weren't sure how, or even whether, malfunction of parkin was involved in the disease.

In the April 23 issue of Science, the Hopkins team reports that nitric oxide (NO) attaches to parkin and reduces its normal ability to mark proteins -- including itself -- for destruction. However, in animal models of PD, there's so much NO on parkin that the protein doesn't work at all. Moreover, NO modification of parkin was two to three times higher in brain tissue from patients with PD than in those without the disease, the researchers report.

"In every tissue sample from patients, the level of NO on parkin was higher than the very highest level measured in brain tissue from people without the disease," says Ted Dawson, M.D., Ph.D., professor of neurology and neuroscience and co-director of the Program for Neural Regeneration and Repair in Hopkins' Institute for Cell Engineering. "This tells us that very effective NO scavengers, ones that cross the blood brain barrier and enter neurons, could be potential drugs to treat Parkinson's disease."

While one doesn't yet exist, such a scavenger should mop up extra NO in the brain, he says, preventing it from blocking parkin's activity. Other wa
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
22-Apr-2004


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