Science Report Illuminates Feedback Circuit In Parkinson's Disease.

NEW YORK – A study published today in the journal Science led by Columbia University Medical Center researcher Asa Abeliovich, MD, PhD, pinpoints a regulatory feedback mechanism within neurons in the midbrain, which is known to deteriorate in brains of people with Parkinson’s disease, a degenerative disorder of the central nervous system that often impairs the sufferer’s motor skills and speech.

The brain region affected by Parkinson’s is also known to play a central role in normal motor control or locomotion (walking) as well as other complex behaviors such as reward and addiction. The neurons in this section of the brain called midbrain dopaminergic neurons (DNs) are known to be regulated by a number of molecules. In this study, researchers identified a novel type of regulatory factor called MicroRNAs within these cells that have a role in midbrain neuron degeneration, the type found in Parkinson’s patients.

To learn more about this process, researchers developed a model using embryonic stem cells. They found that a particular miRNA, called miR-133b, was enriched in the midbrain dopamine neurons and thus was deficient in Parkinson’s disease when these cells are lost. This was the case in both Parkinson’s patients and mouse models of Parkinson’s disease. They also found that miR-133b operates a feedback loop with a brain protein called Pitx3, which is a critical transcription regulator of midbrain dopaminergic neurons.

“We tested this feedback circuit in several different models and our results showed that miR-133b has a profound effect on the development and function of these midbrain neurons,” said Abeliovich, who is an associate professor of pathology and neurology at the Columbia University College of Physicians & Surgeons and also holds appointments at the Taub Institute for the Aging Brain and the Center for Neurobiology and Behavior at Columbia University Medical Center. “We hope to use these findings as a pedestal to look further at microRNAs so that therapeutic targets for neurodegenerative disorders, like Parkinson’s and others, can be identified.”

MicroRNA networks like the one identified in this paper are also linked to other human diseases such as heart disease, cancer, Alzheimer’s disease, and Tourette’s syndrome.

Researchers from the Watson School of Biological Sciences at Cold Spring Harbor Laboratory also contributed to this report.

This study was funded by the Anne and Bernard Spitzer Fund for Cell and Genetic Therapy. The Fund has provided major funding for Columbia's initial efforts in research on neural stem cells, particularly in relation to neurodegenerative diseases, such as Parkinson’s disease.

For statistics and additional information about Parkinson’s disease, visit http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease...

NOTE TO EDITORS: An image of the microRNAs that are lost in Parkinson’s disease is available by request. - ### -

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