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Blocking key enzyme minimizes stroke injury, UT Southwestern research finds
Date:6/26/2014

DALLAS June 26, 2014 A drug that blocks the action of the enzyme Cdk5 could substantially reduce brain damage if administered shortly after a stroke, UT Southwestern Medical Center research suggests.

The findings, reported in the June 11 issue of the Journal of Neuroscience, determined in rodent models that aberrant Cdk5 activity causes nerve cell death during stroke.

"If you inhibit Cdk5, then the vast majority of brain tissue stays alive without oxygen for up to one hour," said Dr. James Bibb, Associate Professor of Neurology and Neurotherapeutics at UT Southwestern and senior author of the study. "This result tells us that Cdk5 is a central player in nerve cell death."

More importantly, development of a Cdk5 inhibitor as an acute neuroprotective therapy has the potential to reduce stroke injury.

"If we could block Cdk5 in patients who have just suffered a stroke, we may be able to reduce the number of patients in our hospitals who become disabled or die from stroke. Doing so would have a major impact on health care," Dr. Bibb said.

While several pharmaceutical companies worked to develop Cdk5 inhibitors years ago, these efforts were largely abandoned since research indicated blocking Cdk5 long-term could have detrimental effects. At the time, many scientists thought aberrant Cdk5 activity played a major role in the development of Alzheimer's disease and that Cdk5 inhibition might be beneficial as a treatment.

Based on Dr. Bibb's research and that of others, Cdk5 has both good and bad effects. When working normally, Cdk5 adds phosphates to other proteins that are important to healthy brain function. On the flip side, researchers have found that aberrant Cdk5 activity contributes to nerve cell death following brain injury and can lead to cancer.

"Cdk5 regulates communication between nerve cells and is essential for proper brain function. Therefore, blocking Cdk5 long-term may not be
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Contact: Debbie Bolles
debbie.bolles@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

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