Sphingosine 1-phosphate signaling at the blood-brain barrier

被引：102
|
作者：
Prager, Briana [1 ]
Spampinato, Simona F. [2 ,3 ]
Ransohoff, Richard M. [1 ,2 ]
机构：
[1] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44195 USA
[2] Cleveland Clin, Lerner Res Inst, Dept Neurosci, Neuroinflannmat Res Ctr, Cleveland, OH 44195 USA
[3] Univ Catania, Pharmacol Sect, Dept Biomed & Biotechnol Sci, Catania, Italy
来源：
TRENDS IN MOLECULAR MEDICINE | 2015年 / 21卷 / 06期
关键词：
sphingosine; 1-phosphate; blood-brain barrier; fingolimod; multiple sclerosis; neuroinflammation; astrocyte; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; SPHINGOSINE-1-PHOSPHATE RECEPTOR 1; ASTROCYTE-ENDOTHELIAL INTERACTIONS; PROTEIN-COUPLED RECEPTOR; MULTIPLE-SCLEROSIS; FINGOLIMOD FTY720; ORAL FINGOLIMOD; VE-CADHERIN; TIGHT JUNCTIONS;
D O I：
10.1016/j.molmed.2015.03.006
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The characterization of molecular pathways that modulate blood-brain barrier (BBB) function and integrity has been fueled by a growing body of literature implicating BBB dysfunction in a wide range of neurologic diseases. Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that has been effectively targeted by the immunomodulatory S1P(1) functional antagonist fingolimod in the treatment of multiple sclerosis (MS). Investigation into the pathways modulated by S1P has revealed its important role in regulating BBB integrity via signaling through receptor isoforms on astrocytes and endothelial cells (ECs). Current evidence supports a significant role for SIP signaling as a key determinant of BBB permeability and hence as a potential pathogenic player or therapeutic target in diseases characterized by BBB dysfunction.
引用
收藏
页码：354 / 363
页数：10
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