Sphingosine-1-phosphate receptor therapies: Advances in clinical trials for CNS-related diseases

摘要

The family of sphingosine-l-phosphate receptors (S1PRs) are G protein-coupled and comprise of five subtypes, S1P(1)-S1P(5). These receptors are activated by the sphingolipid ligand, SIP, which is produced from the phosphorylation of sphingosine by sphingosine kinases. The activation of S1PRs modulates a host of cellular processes such as cell proliferation, migration and survival. These receptors are targeted by the drug fingolimod, a first in class oral therapy for multiple sclerosis. Importantly, S1PRs have also been implicated, in cellular experiments, pre-clinical studies and clinical trials in a range of other neurodegenerative diseases, neurological disorders and psychiatric illnesses, where S1PR drugs are proving beneficial. Overall, studies now highlight the importance of S1PRs as targets for modulating a variety of debilitating brain-related diseases. Here, we review the role of S1PRs in these illnesses.