The Therapeutic Potential of Apoptosis Signal-Regulating

Abstract

Stroke is a worldwide social and economical issue. Ischemic stroke occupies 85 percent of stroke patients and they suffer from disability and other complications such as dementia and paralysis. Despites intensive efforts to rescue stroke patients and expand time window, clinical therapy is limited yet. As well as advanced established method, we need develop novel therapeutic targets for treating ischemic stroke. Apotosis signal-regulating kinase 1 (ASK1) is a member of mitogen activated protein kinase kinase kinase family. ASK1 activates mitogen activated protein kinase kinase and mitogen activated protein kinase family, which is important role in intracellular signaling after various insults from extracellular to intracellular stimuli such as oxidative stress, endoplasmic reticulum stress, osmolality changes and bacterial infection. These are also pathophysiologic factors of cerebral ischemia. In animal model of ischemic stroke, ASK1 is activated under ischemiainduced oxidative stress and apoptosis. ASK1 by silencing with small interfering RNA significantly decreased infarct volume and neuronal cell death. Based on several basic researches, we carefully suggest that inhibition of ASK1 is a novel approach for ischemic stroke therapy.