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Protein Might Mute Effects of Methamphetamine

Manipulation may be used someday against Parkinson's, too, expert suggests.

FRIDAY, May 8 (HealthDay News) -- A protein that appears to lend a hand in the death of brain cells tied to Parkinson's disease might also help fight drug addiction, according to a newly published study.

The protein -- organic cation transporter 3, or oct3 -- normally guides molecules in and out of cells, but it seems to lead the toxic brain chemical MPP+ straight to brain cells, where it kills dopamine neurons, which play a key role in helping people move, the study found in a study in mice.

Dead dopamine neurons are a hallmark of Parkinson's, a degenerative disease known for causing tremors and other motor skill issues.

Scientists at Columbia University and the University of Rochester medical centers in New York found that blocking or genetically removing oct3 in mice kept the MPP+ away from the neurons and holed up inside astrocytes, a common type of brain cell that other researchers have linked to Alzheimer's disease, amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), epilepsy and other neurological afflictions.

"Astrocytes are definitely much more than support cells in the brain," the study's corresponding author, Kim Tieu, an assistant professor in environmental medicine at Rochester, said in a news release issued by Columbia. "Scientists are discovering their involvement in many diseases. The latest results point to their role in Parkinson's disease."

Astrocytes with active oct3 were found in brain tissue the researchers analyzed from people who had died of Parkinson's, they also reported.

MPP+ is the product of another brain chemical, MPTP, that the astrocytes convert. How and why MPP+ leaves the astrocytes has been a mystery to scientists.

The study, published online in the Proceedings of the National Academy of Sciences, does not theorize about what may be the exact cause of Parkinson's disease, which remains a mostly mysterious illness.

During its research, the team also found that oct3 mutes the high that drug users experience from methamphetamines and similar addictive substances. Oct3 helps astrocytes soak up excess dopamine from around neurons. If not done fast or efficiently enough, the residue of dopamine can give people a euphoric feeling while also causing brain damage. Previous research had found that people with low oct3 activity in their brains are more susceptible to drug addiction.

"How you choose to manipulate the function of oct3 depends on the source of the toxic molecules," Tieu said. "You would try to lessen its effects in a condition where it makes a toxic molecule available to vulnerable cells, as illustrated in the current model of Parkinson's disease. But in the case of drug addiction, you might try to increase it, to lessen the impact of a drug like methamphetamine."

Though no drug exists that can block or boost oct3 in people, the researcher said that finding one might eventually aid people with Parkinson's or drug addiction.

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(SOURCE: Columbia University Medical Center, news release, May 4, 2009 )

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