Caveolae: molecular insights and therapeutic targets for stroke

Introduction: Caveolae are specialized plasma membrane micro-invaginations of most mammalian cell types. The organization and function of caveolae are carried out by their coat proteins, caveolins and adaptor proteins, cavins. Caveolae/caveolins physically interact with membrane-associated signaling molecules and function in cholesterol incorporation, signaling transduction and macromolecular transport/permeability. Areas covered: Recent investigations have implicated a check-and-balance role of caveolae in the pathophysiology of cerebral ischemia. Caveolin knockout mice displayed exacerbated ischemic injury, whereas caveolin peptide exerted remarkable protection against ischemia/reperfusion injury. This review attempts to provide a comprehensive synopsis of how caveolae/caveolins modulate blood-brain barrier permeability, pro-survival signaling, angiogenesis and neuroinflammation, and how this may contribute to a better understanding of the participation of caveolae in ischemic cascade. The role of caveolin in the preconditioning-induced tolerance against ischemia is also discussed. Expert opinion: Caveolae represent a novel target for cerebral ischemia. It remains open how to manipulate caveolin expression in a practical way to recapitulate the beneficial therapeutic outcomes. Caveolin peptides and associated antagomirs may be efficacious and deserve further investigations for their potential benefits for stroke.