PMID- 29706868
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 11
DP  - 2018
TI  - The Blood-Brain Barrier and the EphR/Ephrin System: Perspectives on a Link 
      Between Neurovascular and Neuropsychiatric Disorders.
PG  - 127
LID - 10.3389/fnmol.2018.00127 [doi]
LID - 127
AB  - Interactions among endothelial cells (EC) forming blood vessels and their 
      surrounding cell types are essential to establish the blood-brain barrier (BBB), 
      an integral part of the neurovascular unit (NVU). Research on the NVU has 
      recently seen a renaissance to especially understand the neurobiology of vascular 
      and brain pathologies and their frequently occurring comorbidities. Diverse 
      signaling molecules activated in the near proximity of blood vessels trigger 
      paracellular pathways which regulate the formation and stabilization of tight 
      junctions (TJ) between EC and thereby influence BBB permeability. Among 
      regulatory molecules, the erythropoietin-producing-hepatocellular carcinoma 
      receptors (EphR) and their Eph receptor-interacting signals (ephrins) play a 
      pivotal role in EC differentiation, angiogenesis and BBB integrity. Multiple 
      EphR-ligand interactions between EC and other cell types influence different 
      aspects of angiogenesis and BBB formation. Such interactions additionally control 
      BBB sealing properties and thus the penetration of substances into the brain 
      parenchyma. Thus, they play critical roles in the healthy brain and during the 
      pathogenesis of brain disorders. In this mini-review article, we aim at 
      integrating the constantly growing literature about the functional roles of the 
      EphR/ephrin system for the development of the vascular system and the BBB and in 
      the pathogenesis of neurovascular and neuropsychiatric disorders. We suggest the 
      hypothesis that a disrupted EphR/ephrin signaling at the BBB might represent an 
      underappreciated molecular hub of disease comorbidity. Finally, we propose the 
      possibility that the EphR/ephrin system bears the potential of becoming a novel 
      target for the development of alternative therapeutic treatments, focusing on 
      such comorbidities.
FAU - Malik, Victoria A
AU  - Malik VA
AD  - RG Neuro-Glia Pharmacology, Department of Psychiatry and Psychotherapy, 
      University of Regensburg, Regensburg, Germany.
FAU - Di Benedetto, Barbara
AU  - Di Benedetto B
AD  - RG Neuro-Glia Pharmacology, Department of Psychiatry and Psychotherapy, 
      University of Regensburg, Regensburg, Germany.
AD  - Regensburg Center of Neuroscience, University of Regensburg, Regensburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180412
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5906525
OTO - NOTNLM
OT  - EphR/ephrin
OT  - astrocytes
OT  - blood-brain barrier
OT  - endothelial cells
OT  - neuropsychiatric disorders
OT  - neurovascular disorders
EDAT- 2018/05/01 06:00
MHDA- 2018/05/01 06:01
PMCR- 2018/01/01
CRDT- 2018/05/01 06:00
PHST- 2017/10/05 00:00 [received]
PHST- 2018/03/29 00:00 [accepted]
PHST- 2018/05/01 06:00 [entrez]
PHST- 2018/05/01 06:00 [pubmed]
PHST- 2018/05/01 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2018.00127 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2018 Apr 12;11:127. doi: 10.3389/fnmol.2018.00127. 
      eCollection 2018.