Sphingosine 1-phosphate signaling at the blood-brain barrier.
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 S1P1 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 S1P signaling as a key determinant of BBB permeability and hence as a potential pathogenic player or therapeutic target in diseases characterized by BBB dysfunction.
Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Briana
B
Prager
Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy.
Simona F
SF
Spampinato
Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: richard.ransohoff@biogenidec.com.
Richard M
RM
Ransohoff
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002199:Capillary Permeability / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008246:Lysophospholipids / Q000276:immunology / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D049349:Receptors, Lysosphingolipid / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism
D007155:Immunologic Factors; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
astrocyte; blood–brain barrier; fingolimod; multiple sclerosis; neuroinflammation; sphingosine 1-phosphate