From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod.
Epilepsy
S1P receptor
drug repurposing
fingolimod
neuroinflammation
Journal
Current neuropharmacology
ISSN: 1875-6190
Titre abrégé: Curr Neuropharmacol
Pays: United Arab Emirates
ID NLM: 101157239
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
02
2020
revised:
13
03
2020
accepted:
14
04
2020
pubmed:
21
4
2020
medline:
27
7
2021
entrez:
21
4
2020
Statut:
ppublish
Résumé
Epilepsy is a devastating neurological condition characterized by long-term tendency to generate unprovoked seizures, affecting around 1-2 % of the population worldwide. Epilepsy is a serious health concern which often associates with other neurobehavioral comorbidities that further worsen disease conditions. Despite tremendous research, the mainstream anti-epileptic drugs (AEDs) exert only symptomatic relief leading to 30% of untreatable patients. This reflects the complexity of the disease pathogenesis and urges the precise understanding of underlying mechanisms in order to explore novel therapeutic strategies that might alter the disease progression as well as minimize the epilepsy-associated comorbidities. Unfortunately, the development of novel AEDs might be a difficult process engaging huge funds, tremendous scientific efforts and stringent regulatory compliance with a possible chance of end-stage drug failure. Hence, an alternate strategy is drug repurposing, where anti-epileptic effects are elicited from drugs that are already used to treat non-epileptic disorders. Herein, we provide evidence of the anti-epileptic effects of Fingolimod (FTY720), a modulator of sphingosine-1-phosphate (S1P) receptor, USFDA approved already for Relapsing-Remitting Multiple Sclerosis (RRMS). Emerging experimental findings suggest that Fingolimod treatment exerts disease-modifying anti-epileptic effects based on its anti-neuroinflammatory properties, potent neuroprotection, anti-gliotic effects, myelin protection, reduction of mTOR signaling pathway and activation of microglia and astrocytes. We further discuss the underlying molecular crosstalk associated with the anti-epileptic effects of Fingolimod and provide evidence for repurposing Fingolimod to overcome the limitations of current AEDs.
Identifiants
pubmed: 32310049
pii: CN-EPUB-105931
doi: 10.2174/1570159X18666200420125017
pmc: PMC7709153
doi:
Substances chimiques
Anticonvulsants
0
Sphingosine 1 Phosphate Receptor Modulators
0
Fingolimod Hydrochloride
G926EC510T
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1126-1137Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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