Mice lacking AEP protease show reduced apoptosis after stroke, according to Molecular Cell study.

The protease asparagine endopeptidase (AEP) unleashes enzymes that break down brain cells’ DNA after a stroke or a seizure, report scientists at Emory University School of Medicine.

When a stroke obstructs blood flow to part of the brain, the lack of oxygen causes a buildup of lactic acid, the same chemical that appears in the muscles during intense exercise. In addition, a flood of chemicals that brain cells usually use to communicate with each other overexcites the cells. Epileptic seizures can have similar effects. While some brain cells die directly because of lack of oxygen, others undergo programmed cell death.

The researchers began by looking for proteins that stick to another protein called PIKE-L, which they previously had studied because of its ability to interfere with programmed cell death in brain cells. They discovered that PIKE-L sticks to SET, a protein that regulates DNA-eating enzymes involved in programmed cell death. In addition, the team found that PIKE-L appears to protect SET from attack by AEP.

Furthermore in mice genetically engineered to lack AEP, both a drug that mimics the acidic overload induced by stroke and an artificial stroke resulted in reduced DNA damage and less brain cell death than in regular mice.

The results are published in the March 28 issue of Molecular Cell.

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