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
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
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