KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation

Pharmacological modulation of ATP-sensitive potassium channels has become a promising new therapeutic approach for the treatment of neurodegenerative diseases due to their role in mitochondrial and cellular protection. For instance, diazoxide, a well-known ATP-sensitive potassium channel activator w...

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Detalhes bibliográficos
Autores: Virgili, Noemi, Mancera, Pilar, Wappenhans, Blanca, Sorrosal, Georgina, Biber, Knut, Pugliese, Marco, Espinosa Parrilla, Juan Francisco
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/175179
Acesso em linha:https://hdl.handle.net/2445/175179
Access Level:acceso abierto
Palavra-chave:Esclerosi múltiple
Malalties neurodegeneratives
Antioxidants
Multiple sclerosis
Neurodegenerative Diseases
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spelling KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway ActivationVirgili, NoemiMancera, PilarWappenhans, BlancaSorrosal, GeorginaBiber, KnutPugliese, MarcoEspinosa Parrilla, Juan FranciscoEsclerosi múltipleMalalties neurodegenerativesAntioxidantsMultiple sclerosisNeurodegenerative DiseasesAntioxidantsPharmacological modulation of ATP-sensitive potassium channels has become a promising new therapeutic approach for the treatment of neurodegenerative diseases due to their role in mitochondrial and cellular protection. For instance, diazoxide, a well-known ATP-sensitive potassium channel activator with high affinity for mitochondrial component of the channel has been proved to be effective in animal models for different diseases such as Alzheimer's disease, stroke or multiple sclerosis. Here, we analyzed the ability of diazoxide for protecting neurons front different neurotoxic insults in vitro and ex vivo. Results showed that diazoxide effectively protects NSC-34 motoneurons from glutamatergic, oxidative and inflammatory damage. Moreover, diazoxide decreased neuronal death in organotypic hippocampal slice cultures after exicitotoxicity and preserved myelin sheath in organotypic cerebellar cultures exposed to pro-inflammatory demyelinating damage. In addition, we demonstrated that one of the mechanisms of actions implied in the neuroprotective role of diazoxide is mediated by the activation of Nrf2 expression and nuclear translocation. Nrf2 expression was increased in NSC-34 neurons in vitro as well as in the spinal cord of experimental autoimmune encephalomyelitis animals orally administered with diazoxide. Thus, diazoxide is a neuroprotective agent against oxidative stress-induced damage and cellular dysfunction that can be beneficial for diseases such as multiple sclerosis.Public Library of Science (PLoS)2021202120132021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/175179Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0075189PLoS One, 2013, vol. 8, num. 9, p. e75189https://doi.org/10.1371/journal.pone.0075189cc-by (c) Virgili, Noemi et al., 2013http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1751792026-05-29T05:05:01Z
dc.title.none.fl_str_mv KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation
title KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation
spellingShingle KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation
Virgili, Noemi
Esclerosi múltiple
Malalties neurodegeneratives
Antioxidants
Multiple sclerosis
Neurodegenerative Diseases
Antioxidants
title_short KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation
title_full KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation
title_fullStr KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation
title_full_unstemmed KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation
title_sort KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation
dc.creator.none.fl_str_mv Virgili, Noemi
Mancera, Pilar
Wappenhans, Blanca
Sorrosal, Georgina
Biber, Knut
Pugliese, Marco
Espinosa Parrilla, Juan Francisco
author Virgili, Noemi
author_facet Virgili, Noemi
Mancera, Pilar
Wappenhans, Blanca
Sorrosal, Georgina
Biber, Knut
Pugliese, Marco
Espinosa Parrilla, Juan Francisco
author_role author
author2 Mancera, Pilar
Wappenhans, Blanca
Sorrosal, Georgina
Biber, Knut
Pugliese, Marco
Espinosa Parrilla, Juan Francisco
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Esclerosi múltiple
Malalties neurodegeneratives
Antioxidants
Multiple sclerosis
Neurodegenerative Diseases
Antioxidants
topic Esclerosi múltiple
Malalties neurodegeneratives
Antioxidants
Multiple sclerosis
Neurodegenerative Diseases
Antioxidants
description Pharmacological modulation of ATP-sensitive potassium channels has become a promising new therapeutic approach for the treatment of neurodegenerative diseases due to their role in mitochondrial and cellular protection. For instance, diazoxide, a well-known ATP-sensitive potassium channel activator with high affinity for mitochondrial component of the channel has been proved to be effective in animal models for different diseases such as Alzheimer's disease, stroke or multiple sclerosis. Here, we analyzed the ability of diazoxide for protecting neurons front different neurotoxic insults in vitro and ex vivo. Results showed that diazoxide effectively protects NSC-34 motoneurons from glutamatergic, oxidative and inflammatory damage. Moreover, diazoxide decreased neuronal death in organotypic hippocampal slice cultures after exicitotoxicity and preserved myelin sheath in organotypic cerebellar cultures exposed to pro-inflammatory demyelinating damage. In addition, we demonstrated that one of the mechanisms of actions implied in the neuroprotective role of diazoxide is mediated by the activation of Nrf2 expression and nuclear translocation. Nrf2 expression was increased in NSC-34 neurons in vitro as well as in the spinal cord of experimental autoimmune encephalomyelitis animals orally administered with diazoxide. Thus, diazoxide is a neuroprotective agent against oxidative stress-induced damage and cellular dysfunction that can be beneficial for diseases such as multiple sclerosis.
publishDate 2013
dc.date.none.fl_str_mv 2013
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/175179
url https://hdl.handle.net/2445/175179
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0075189
PLoS One, 2013, vol. 8, num. 9, p. e75189
https://doi.org/10.1371/journal.pone.0075189
dc.rights.none.fl_str_mv cc-by (c) Virgili, Noemi et al., 2013
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Virgili, Noemi et al., 2013
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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