Positive allosteric modulation of alpha7 nicotinic acetylcholine receptors as a novel approach to treatment of ischemic stroke

Abstract

Ischemic stroke is a leading cause of disability and death worldwide. Despite substantial investments in developing anti-stroke medicines, clinically effective pharmacological treatments remain inadequate. Clinical utility of tissue plasminogen activator (tPA, Alteplase), the only FDA-approved drug treatment is limited (72 h) intravenous (i.v.) or subcutaneous (s.c.) administration of PNU significantly reduced brain injury and neurological deficits after MCAO. The therapeutic efficacy of PNU after stroke may arise from activation of multiple converging α7-dependent therapeutic pathways including direct cytoprotection and central/peripheral anti-inflammatory mechanisms and may hold significant translational potential. Our results may become a starting point for developing clinically efficacious therapies utilizing α7 agents and may enable health-care providers to overcome limitations linked to the lack of effective treatments after stroke