We observed that this NRF2-HIF1α signaling loop plays a dual role in stroke settings: First in p62-mediated protection of neuronal cells via NRF2 signaling and secondly in ROS-induced apoptotic cell death since chemical inhibition of HIF1α strongly diminished Reox-induced apoptosis suggesting HIF1α may be involved in detrimental ROS formation. This evidence concerns the gene SQSTM1 and stroke disorder.