Brain sphingosine-1-phosphate receptors: implication for FTY720 in the treatment of multiple sclerosis.
Multiple sclerosis (MS) is an autoimmune, neurological disability with unknown etiology. The current therapies available for MS work by an immunomodulatory action, preventing T-cell- and macrophage-mediated destruction of brain-resident oligodendrocytes and axonal loss. Recently, FTY720 (fingolimod) was shown to significantly reduce relapse rates in MS patients and is currently in Phase III clinical trials. This drug attenuates trafficking of harmful T cells entering the brain by regulating sphingosine-1-phosphate (S1P) receptors. Here, we outline the direct roles that S1P receptors play in the central nervous system (CNS) and discuss additional modalities by which FTY720 may provide direct neuroprotection in MS.
Dev
Kumlesh K
KK
Department of Anatomy and Neuroscience, University College Cork, Windle Building, Cork, Ireland. k.dev@ucc.ie
Mullershausen
Florian
F
Mattes
Henri
H
Kuhn
Rainer R
RR
Bilbe
Graeme
G
Hoyer
Daniel
D
Mir
Anis
A
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D016503:Drug Delivery Systems; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D049349:Receptors, Lysosphingolipid / Q000187:drug effects / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine