Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation

Fluids and Barriers of the CNS

Pierre-Olivier Couraud¹  Kayathiri Ganeshamoorthy¹  Fabienne Glacial¹  Cédric Artus¹  Anny-Claude Luissint¹ 

[1] Université Paris Descartes, Sorbonne Paris Cité, Paris, France

关键词: Signaling pathways;    Kinases;    Neurovascular unit;    Tight junction;    Blood–brain barrier;   

Others  :  807095
DOI  :  10.1186/2045-8118-9-23

 received in 2012-07-03, accepted in 2012-10-21,  发布年份 2012

【 摘 要 】

The Blood–brain barrier (BBB), present at the level of the endothelium of cerebral blood vessels, selectively restricts the blood-to-brain paracellular diffusion of compounds; it is mandatory for cerebral homeostasis and proper neuronal function. The barrier properties of these specialized endothelial cells notably depend on tight junctions (TJs) between adjacent cells: TJs are dynamic structures consisting of a number of transmembrane and membrane-associated cytoplasmic proteins, which are assembled in a multimolecular complex and acting as a platform for intracellular signaling. Although the structural composition of these complexes has been well described in the recent years, our knowledge about their functional regulation still remains fragmentary. Importantly, pericytes, embedded in the vascular basement membrane, and perivascular microglial cells, astrocytes and neurons contribute to the regulation of endothelial TJs and BBB function, altogether constituting the so-called neurovascular unit.

The present review summarizes our current understanding of the structure and functional regulation of endothelial TJs at the BBB. Accumulating evidence points to a correlation between BBB dysfunction, alteration of TJ complexes and progression of a variety of CNS diseases, such as stroke, multiple sclerosis and brain tumors, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s diseases. Understanding how TJ integrity is controlled may thus help improve drug delivery across the BBB and the design of therapeutic strategies for neurological disorders.

【 授权许可】

   
2012 Luissint et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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