Tight junctions at the blood brain barrier physiological architecture and disease-associated dysregulation 英文参考文献.docVIP

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Tight junctions at the blood brain barrier physiological architecture and disease-associated dysregulation 英文参考文献.doc

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Tight junctions at the blood brain barrier physiological architecture and disease-associated dysregulation 英文参考文献

Luissintetal.FluidsandBarriersoftheCNS2012,9:23 /content/9/1/23 FLUIDS AND BARRIERS OF THE CNS REVIEW OpenAccess Tightjunctionsatthebloodbrainbarrier: physiologicalarchitectureanddisease-associated dysregulation Anny-ClaudeLuissint1,2,3,CédricArtus1,2,3,FabienneGlacial1,2,3,KayathiriGaneshamoorthy1,2,3 andPierre-OlivierCouraud1,2,3* Abstract TheBlood–brainbarrier(BBB),presentattheleveloftheendotheliumofcerebralbloodvessels,selectivelyrestricts theblood-to-brainparacellulardiffusionofcompounds;itismandatoryforcerebralhomeostasisandproper neuronalfunction.Thebarrierpropertiesofthesespecializedendothelialcellsnotablydependontightjunctions (TJs)betweenadjacentcells:TJsaredynamicstructuresconsistingofanumberoftransmembraneand membrane-associatedcytoplasmicproteins,whichareassembledinamultimolecularcomplexandactingasa platformforintracellularsignaling.Althoughthestructuralcompositionofthesecomplexeshasbeenwell describedintherecentyears,ourknowledgeabouttheirfunctionalregulationstillremainsfragmentary. Importantly,pericytes,embeddedinthevascularbasementmembrane,andperivascularmicroglialcells,astrocytes andneuronscontributetotheregulationofendothelialTJsandBBBfunction,altogetherconstitutingtheso-called neurovascularunit. Thepresentreviewsummarizesourcurrentunderstandingofthestructureandfunctionalregulationofendothelial TJsattheBBB.AccumulatingevidencepointstoacorrelationbetweenBBBdysfunction,alterationofTJcomplexes andprogressionofavarietyofCNSdiseases,suchasstroke,multiplesclerosisandbraintumors,aswellas neurodegenerativediseaseslikeParkinson’sandAlzheimer’sdiseases.UnderstandinghowTJintegrityiscontrolled maythushelpimprovedrugdeliveryacrosstheBBBandthedesignoftherapeuticstrategiesforneurological disorders. Keywords:Blood–brainbarrier,Tightjunction,Neurovascularunit,Kinases,Signalingpathways Review Background altogether constitute the neurovascular unit (NVU), a concept highlighting the functional cell-cell interactions The BBB maintains the homeostasis of the central