Caveolae: molecular insights and therapeutic targets for stroke

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

Acknowledgment

L Xu and R Guo have equally contributed to this work.

Declaration of interest

This work was supported by National Natural Science Foundation of China (NFSC) (No. 31300900, 81471182, 81200892, 31100784 and 81400332) and Military Medicine Key Program (BWS12J015). Writing assistance from Medsci Inc. was utilized in the production of the manuscript and was funded by NSFC funding. All authors declare no conflict of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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