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The Sphingosine 1-Phosphate Signaling Pathway in Epilepsy: A Possible Role for the Immunomodulator Drug Fingolimod in Epilepsy Treatment

Leo, A; Citraro, R; Marra, R; Palma, E; Di Paola, ED; Constanti, A; De Sarro, G; (2017) The Sphingosine 1-Phosphate Signaling Pathway in Epilepsy: A Possible Role for the Immunomodulator Drug Fingolimod in Epilepsy Treatment. CNS & Neurological Disorders - Drug Targets , 16 (3) pp. 311-325. 10.2174/1871527315666161104163031. Green open access

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Abstract

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.

Type: Article
Title: The Sphingosine 1-Phosphate Signaling Pathway in Epilepsy: A Possible Role for the Immunomodulator Drug Fingolimod in Epilepsy Treatment
Open access status: An open access version is available from UCL Discovery
DOI: 10.2174/1871527315666161104163031
Publisher version: https://doi.org/10.2174/1871527315666161104163031
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Sphingosine 1-phosphate (S1P) signaling; Fingolimod; Neuroinflammation; Neurodegeneration; Central nervous system diseases; Seizures; Epilepsy; Epileptogenesis
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1570667
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