eprintid: 1570667
rev_number: 29
eprint_status: archive
userid: 608
dir: disk0/01/57/06/67
datestamp: 2017-08-20 00:19:43
lastmod: 2021-12-17 22:59:09
status_changed: 2017-09-15 18:08:11
type: article
metadata_visibility: show
creators_name: Leo, A
creators_name: Citraro, R
creators_name: Marra, R
creators_name: Palma, E
creators_name: Di Paola, ED
creators_name: Constanti, A
creators_name: De Sarro, G
creators_name: Russo, E
title: The Sphingosine 1-Phosphate Signaling Pathway in Epilepsy: A Possible Role for the Immunomodulator Drug Fingolimod in Epilepsy Treatment
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D10
divisions: G10
keywords: Sphingosine 1-phosphate (S1P) signaling; Fingolimod; Neuroinflammation; Neurodegeneration; Central nervous system diseases; Seizures; Epilepsy; Epileptogenesis
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2017
date_type: published
publisher: BENTHAM SCIENCE PUBL
official_url: https://doi.org/10.2174/1871527315666161104163031
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
article_type_text: Review
verified: verified_manual
elements_id: 1413319
doi: 10.2174/1871527315666161104163031
lyricists_name: Constanti, Andrew
lyricists_id: ACONS16
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: CNS & Neurological Disorders - Drug Targets
volume: 16
number: 3
pagerange: 311-325
pages: 15
issn: 1996-3181
citation:        Leo, A;    Citraro, R;    Marra, R;    Palma, E;    Di Paola, ED;    Constanti, A;    De Sarro, G;           Leo, A;  Citraro, R;  Marra, R;  Palma, E;  Di Paola, ED;  Constanti, A;  De Sarro, G;  Russo, E;   - view fewer <#>    (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 <https://doi.org/10.2174/1871527315666161104163031>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1570667/1/Leo_Sphingosine_1-Phosphate.pdf