The role of the sigma-1 receptor in neuroprotection: Comment on Nrf-2 as a therapeutic target in ischemic stroke

摘要

Acute ischemic stroke (AIS) is a significant cause of mortality worldwide and causes long term disability in those that survive the initial event. AIS causes damage to the brain when a blockage occurs in the cerebral arteries causing starvation of oxygen and nutrients to the brain cells. The key intervention for AIS is the removal of the blockage either by thrombotic agent or thrombectomy, without delay. Along with the removal of the blockage, treatments to repair or prevent further damage to neurons in that region of the brain are a feature of much research into AIS. Targeting multiple targets or using drugs with pleiotropic actions on multiple pathways could be the key to treating neurological diseases including AIS. We recently read the editorial by Mazur et al. 1, which elegantly brings together data highlighting the role of Nrf2 in the central nervous system. It discusses how, with the help of upstream regulators such as protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and phosphoinositide 3-kinases (PI3K), it can be targeted in the acute treatment of AIS. However, the authors neglect to discuss the role of the sigma-1 receptor (o-1R) in Nrf2 activation, and how activation of the o-1R may have pleiotropic actions involving Nrf2 and other pathways beneficial to the treatment of neurological diseases including AIS.