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 a part of the brain, the lack of oxygen causes a buildup of lactic acid. Epileptic seizures can have similar effects. While some brain cells die directly because of lack of oxygen, others undergo programmed cell death.

The researchers discovered that AEP is activated under acidic conditions and that it cuts SET, an inhibitor of DNase enzymes involved in programmed cell death. This in turn triggers acid-induced apoptosis. In addition, the team found that PIKE-L, a protein previously known to interfere with programmed cell death, prevents AEP from cutting SET.

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

Contributions also came from researchers at Harvard Medical School, University of Dundee, and Kanazawa University. The results will be published in the March 28 issue of Molecular Cell.

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