title: Sphingosin-1-phosphate Receptor 1: a Potential Target to Inhibit Neuroinflammation and Restore the Sphingosin-1-phosphate Metabolism.
abstract: BACKGROUND
  Recent evidence suggests that an extreme shift may occur in sphingosine metabolism in neuroinflammatory contexts. Sphingosine 1-phosphate (S1P)-metabolizing enzymes (SMEs) regulate the level of S1P. We recently found that FTY720, a S1P analogue, and SEW2871, a selective S1P receptor 1 (S1P1) agonist, provide protection against neural damage and memory deficit in amyloid beta (Aβ)-injected animals. This study aimed to evaluate the effects of these two analogues on the expression of SMEs as well as their anti-inflammatory roles.
  
  
  METHODS
  Rats were treated with intracerebral lipopolysaccharide (LPS) or Aβ. Memory impairment was assessed by Morris water maze and the effects of drugs on SMEs as well as inflammatory markers, TNF- α and COX-II, were determined by immunoblotting.
  
  
  RESULTS
  Aβ and LPS differentially altered the expression profile of SMEs. In Aβ-injected animals, FTY720 and SEW2871 treatments exerted anti-inflammatory effects and restored the expression profile of SMEs, in parallel to our previous findings. In LPS animals however, in spite of anti-inflammatory effects of the two analogues, only FTY720 restored the levels of SMEs and prevented memory deficit.
  
  
  CONCLUSIONS
  The observed ameliorating effects of FTY720 and SEW7821 can be partly attributed to the interruption of the vicious cycle of abnormal S1P metabolism and neuro-inflammation. The close imitation of the FTY720 effects by SW2871 in Aβ-induced neuro-inflammation may highlight the attractive role of S1P1 as a potential target to restore S1P metabolism and inhibit inflammatory processes.
authors: 1Neuroscience Research Center,Shahid Beheshti University of Medical Sciences,Teheran.
authors: Zeynab
authors: Z
authors: Kolahdooz
authors: 2Department of Pharmacology and Toxicology, Faculty of Pharmacy,Shahid Beheshti University of Medical Sciences,Teheran.
authors: Sanaz
authors: S
authors: Nasoohi
authors: 4Department of Biology, Faculty of Basic and Medical Sciences,Zanjan Branch,Islamic Azad University,Zanjan,Iran.
authors: Masoumeh
authors: M
authors: Asle-Rousta
authors: 1Neuroscience Research Center,Shahid Beheshti University of Medical Sciences,Teheran.
authors: Abolhassan
authors: A
authors: Ahmadiani
authors: 3NeuroBiology Research Center,Shahid Beheshti University of Medical Sciences,Teheran.
authors: Leila
authors: L
authors: Dargahi
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D010069:Oxadiazoles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid; C503964:SEW2871; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; C060506:sphingosine 1-phosphate; D051546:Cyclooxygenase 2; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: S1P1 receptor