Spingolipids in Multiple Sclerosis.
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system, mainly affecting young adults. Current therapeutic approaches focus on the suppression of the immune system and on blockade of T cell blood-brain barrier transmigration into the brain parenchyma. Recently, sphingolipids that have been linked to MS pathophysiology, i.e., Sphingosine-1-phosphate (S1P), intracellularly produced lysophospholipids, can be recognized by receptors located on T and B cells. The recent demonstration that S1P is able to direct lymphocyte trafficking between blood and lymphoid system has been translated into therapeutic application: A S1P analogue, FTY720, is currently under clinical investigation in MS. Further cell membrane lipids that are involved in cell proliferation, signalling cascades and apoptosis might be of relevance in MS pathophysiology and, thus, await further investigation. This review focuses on the current knowledge on the role of sphingolipids in MS and discusses their potential therapeutical implications.
Walter
Silke
S
Department of Neurology, University of the Saarland, Homburg, Germany.
Fassbender
Klaus
K
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D009103:Multiple Sclerosis / Q000209:etiology*; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D005732:Gangliosides; D013107:Sphingolipids; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine