Inhibition of DAPK‐1 induces neuronal cell rescue which is linked to ER stress in stroke animal model (877.16)

Abstract

Background: Death associated protein kinase (DAPK) was identified as key player of multiple cell death. DAPK‐1 related apoptosis is the prototypic member of DAPK family that is activated by signaling pathway such as endoplasmic reticulum (ER) stress. Activation of ER stress response has been found to be associated with neurodegenerative disease. ER stress by the unfolded protein response interfere ER homeostasis and promotes neuronal cell death.Purpose: Here, we are going to determine that cerebral ischemia induces ER stress by reperfusion brain injury following middle cerebral artery occlusion (MCAo) in rats. Additionally, we tried to identify that DAPK‐1 is an essential component in the programmed cell death pathway.Results: Focal cerebral ischemic rats by MCAo are exhibited ER stress response and neuronal cell death. However, brain injury volume was reduced in MCAo rats treated with DAPK inhibitor compared to MCAo vehicles suggesting inhibition of DAPK has not only protective effect on neuronal cells death but also resistant to cerebral ischemic injury.Suggestion: Accordingly, DAPK linked to ER stress may regulate the neuronal cell death. Furthermore, down regulation of DAPK represents a potential therapeutic target for transient focal ischemia and neurodegenerative diseases.