Caveolae: molecular insights and therapeutic targets for stroke

Expert Opin Ther Targets. 2015 May;19(5):633-50. doi: 10.1517/14728222.2015.1009446. Epub 2015 Feb 2.

Abstract

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.

Keywords: caveolae; caveolin; cerebral ischemia; pro-survival signaling; stroke.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / physiopathology
  • Caveolae / metabolism*
  • Caveolins / genetics
  • Caveolins / metabolism
  • Drug Design
  • Humans
  • Mice
  • Molecular Targeted Therapy
  • Reperfusion Injury / physiopathology
  • Signal Transduction / drug effects
  • Stroke / drug therapy*
  • Stroke / physiopathology

Substances

  • Caveolins