Protein Linked To Post-Stroke Brain Cell Damage

A recent study by the Emory University School of Medicine found that the protein asparagine endopeptidase (AEP) is responsible for unleashing enzymes that destroy brain cells’ DNA after a stroke.  According to researchers, the findings may assist doctors in limiting post-stroke permanent brain damage by creating drugs that block AEP.

When a stroke occurs, many brain cells die due to lack of oxygen.  However, others undergo a “programmed cell death,” during which a buildup of lactic acid triggers cells to destroy their own DNA.

“The mystery was: how do the acidic conditions trigger DNA damage?” says senior author Keqiang Ye, PhD.  “This was a very surprising result because previously we had no idea that AEP was involved in this process,” Ye added.

Ye and the other researchers initially believed that another class of proteases called caspases controlled DNA damage after a stroke.  In fact, they even thought that early experimental results showing AEP to control post-stroke cell damage were a mistake.  However, further tests proved otherwise.

When the researchers mimicked acidic overload, they found AEP was activated and then broke down DNA in brain cells. Additional experiments were conducted with mice genetically engineered to lack AEP.  When artificial strokes were induced, the mice had reduced DNA damage and less brain cell loss than mice with normal levels of AEP.

The totality of these results lead researchers to believe, “that AEP might be the major proteinase mediating this devastating process.”

For further information: “Neuroprotective Actions of PIKE-L by Inhibition of SET Proteolytic Degradation by Asparagine Endopeptidase,” Molecular Cell, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Vol 29, March 28, 2008.