The Sphingosine 1-Phosphate Signaling Pathway in Epilepsy: A Possible Role for the Immunomodulator Drug Fingolimod in Epilepsy Treatment.
It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G proteincoupled S1P receptor. Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying therapy that has been approved for the treatment of multiple sclerosis. Magnetic resonance imaging data suggest that fingolimod may be effective in multiple sclerosis by preventing blood-brain barrier disruption and brain atrophy. Fingolimod might also possess S1P receptorindependent effects and exerts both anti-inflammatory and neuroprotective effects. In the therapeutic management of epilepsy, there are a great number of antiepileptic drugs, but there is still a need for others that are more effective and safer. S1P and its receptors might represent a suitable novel target also in light of their involvement in neuroinflammation, a well-known process underlying seizures and epileptogenesis. The objective of this manuscript is to review the biological role of S1P and its receptors, focusing on their expression, effects and possible involvement in epilepsy; furthermore, we summarize the possible anti-seizure properties of fingolimod and discuss its possible usefulness in epilepsy treatment. We conclude that fingolimod, being already commercially available, might be easily tested for its possible therapeutic effectiveness in epileptic patients, both after a more comprehensive evaluation of the real potential of this drug and following a clear evaluation of the potential role of its main targets, including the S1P signaling pathway in epilepsy.
Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Catanzaro. Italy.
Antonio
A
Leo
Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Catanzaro. Italy.
Rita
R
Citraro
National Council of Research (CNR), Institute of Neurological Science, Catanzaro. Italy.
Rosario
R
Marra
Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Catanzaro. Italy.
Ernesto
E
Palma
Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Catanzaro. Italy.
Eugenio Di Donato
EDD
Paola
Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, London. United Kingdom.
Andrew
A
Constanti
Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Catanzaro. Italy.
Giovambattista
G
De Sarro
Science of Health Department, School of Medicine, University of Catanzaro, Via T. Campanella, 115, 88100 Catanzaro. Italy.
Emilio
E
Russo
D000818:Animals; D004827:Epilepsy / Q000188:drug therapy*; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008246:Lysophospholipids / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D007155:Immunologic Factors; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
Central nervous system diseases; epilepsy; epileptogenesis; fingolimod; neurodegeneration; neuroinflammation; seizures; sphingosine 1-phosphate (S1P) signaling