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From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod

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 co...

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Autores principales: Paudel, Yam Nath, Angelopoulou, Efthalia, Piperi, Christina, Gnatkovsky, Vadym, Othman, Iekhsan, Shaikh, Mohd. Farooq
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709153/
https://www.ncbi.nlm.nih.gov/pubmed/32310049
http://dx.doi.org/10.2174/1570159X18666200420125017
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author Paudel, Yam Nath
Angelopoulou, Efthalia
Piperi, Christina
Gnatkovsky, Vadym
Othman, Iekhsan
Shaikh, Mohd. Farooq
author_facet Paudel, Yam Nath
Angelopoulou, Efthalia
Piperi, Christina
Gnatkovsky, Vadym
Othman, Iekhsan
Shaikh, Mohd. Farooq
author_sort Paudel, Yam Nath
collection PubMed
description 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.
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spelling pubmed-77091532021-05-01 From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod Paudel, Yam Nath Angelopoulou, Efthalia Piperi, Christina Gnatkovsky, Vadym Othman, Iekhsan Shaikh, Mohd. Farooq Curr Neuropharmacol Article 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. Bentham Science Publishers 2020-11 2020-11 /pmc/articles/PMC7709153/ /pubmed/32310049 http://dx.doi.org/10.2174/1570159X18666200420125017 Text en © 2020 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/legalcode This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Paudel, Yam Nath
Angelopoulou, Efthalia
Piperi, Christina
Gnatkovsky, Vadym
Othman, Iekhsan
Shaikh, Mohd. Farooq
From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod
title From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod
title_full From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod
title_fullStr From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod
title_full_unstemmed From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod
title_short From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod
title_sort from the molecular mechanism to pre-clinical results: anti-epileptic effects of fingolimod
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709153/
https://www.ncbi.nlm.nih.gov/pubmed/32310049
http://dx.doi.org/10.2174/1570159X18666200420125017
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