The emerging role of FTY720 as a sphingosine 1 ‐phosphate analog for the treatment of ischemic stroke: The cellular and molecular mechanisms

Three important mechanisms for neuroprotective effects of FTY720 have been described. Functional antagonistic, functional agonistic and receptor-independent mechanisms. Here, we review these mechanisms in more details and describe animal model and in clinical trial studies AbstractFinding novel and effective drugs for the treatment of ischemic stroke is warranted because there is not a definitive treatment for this prevalent disease. Due to the relevance between the sphingosine 1-phosphate (S1P) receptor and several neurological diseases including ischemic stroke, it seems that fingolimod (FTY720), as an agonist of S1P receptor, can be a useful therapeutic strategy in these patients. FTY720 is the first oral drug approved by the US food and drug administration for the treatment of multiple sclerosis. Three important mechanisms for neuroprotective effects of FTY720 have been described. First, the functional antagonistic mechanism that is associated with lymphopenia and reduced lymphocytic inflammation. This effect results from the down-regulation and degradation of lymphocytes' S1P receptors, which inhibits lymph node lymphocytes from entering the bloodstream. Second, a functional agonistic activity that is mediated through direct effects via targeting S1P receptors on the membrane of various cells including neurons, microglia, oligodendrocytes, astrocytes, and endothelial cells of blood vessels in the central nervous system (CNS), and the third, receptor-independent mechanism...
Source: Brain and Behavior - Category: Neurology Authors: Tags: REVIEW Source Type: research