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Science News

PDF Interprets: Protein Channels Toxic Chemical to Neurons

Could the same protein that helps to fight certain drug addictions play a role in Parkinson's disease (PD)? 

Researchers at Columbia University and the University of Rochester, led by Kim Tieu, Ph.D., suspect the culprit protein, called Oct3, may cause the death of dopamine neurons in Parkinson's.  The death of dopamine neurons in the substantia nigra is a hallmark of Parkinson's, which causes its motor symptoms.

The study, recently published in the April 29 online edition of the Proceedings of the National Academy of Sciences, found that cells in the brain known as astrocytes, which surround neurons and often help to keep them healthy, can sometimes harbor toxic molecules.  A protein, called organic cation transporter-3 (Oct3), can ferry the toxic molecules from inside the astrocytes to the border of dopamine neurons. 

Once there, Oct3 hands off the molecules to other transporter molecules, which carry them into the neurons, causing their death.

The scientists studied mice with Parkinsonian symptoms that had been exposed to the chemical MPTP.  In astrocytes, MPTP is converted to the toxic cation MPP+. When Oct3 was present in the usual amounts in the mice, dopamine neurons died as expected.  But when the scientists blocked or genetically removed Oct3 in mice, MPP+ remained sequestered inside astrocytes and did not affect the dopamine neurons.

Researchers also found astrocytes with active Oct3 in brain tissue analyzed from people who had died with Parkinson’s. 

The researchers hypothesize that Oct3 transports cations associated with cell death in people with Parkinson’s in the same way, and suggest that therapies to block Oct3 activity might protect dopamine neurons. Oct3 is also implicated in the brain mechanisms leading to addiction and depression, so drugs targeting the molecule could have wide-ranging uses.

Lead researcher, Kim Tieu, Ph.D., initiated this study while a postdoctoral research associate in the laboratory of Serge Przedborski, M.D., Ph.D., the Page and William Black Professor of Neurology at Columbia University.  The work of Dr. Przedborski, who was also an author of the study, is supported by PDF’s annual Center Grant to Columbia University.

Source Date: May 18 2009