Intervention of Death-Associated Protein Kinase 1–p53 Interaction Exerts the Therapeutic Effects Against Stroke
Background and Purpose—Death-associated protein kinase 1 (DAPK1) interacts with the tumor suppressor gene p53 via a direct binding of a death domain of DAPK1 to a DNA-binding motif (DM) of p53 (p53DM) and converges multiple cell death pathways in stroke. The goals of this study are to determine whether disruption of DAPK1–p53 interaction is therapeutically effective against stroke.
Methods—We synthesized a membrane-permeable p53DM peptide (Tat-p53DM) and tested the therapeutic effects of Tat-p53DM in a mouse model with stroke.
Results—We showed that Tat-p53DM blocked DAPK1–p53 interaction in brain cells in vivo. When administered 6 hours after stroke onset in adult male mice, Tat-p53DM was still therapeutically effective against brain damages and improved neurological functions.
Conclusions—DAPK1–p53 interaction is a preferred target for therapeutic intervention of stroke.
- Received June 5, 2014.
- Revision received July 17, 2014.
- Accepted July 28, 2014.
- © 2014 American Heart Association, Inc.