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A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease

The orphan drug dantrolene (DAN) is the only therapeutic treatment for malignant hyperthermia (MH), a pharmacogenetic pathology affecting 0.2 over 10,000 people in the EU. It acts by inhibiting ryanodine receptors, which are responsible for calcium recruitment in striatal muscles and brain. Because...

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Autores principales: Bolognino, Isabella, Giangregorio, Nicola, Pisani, Leonardo, de Candia, Modesto, Purgatorio, Rosa, Tonazzi, Annamaria, Altomare, Cosimo Damiano, Cellamare, Saverio, Catto, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930524/
https://www.ncbi.nlm.nih.gov/pubmed/31775359
http://dx.doi.org/10.3390/molecules24234298
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author Bolognino, Isabella
Giangregorio, Nicola
Pisani, Leonardo
de Candia, Modesto
Purgatorio, Rosa
Tonazzi, Annamaria
Altomare, Cosimo Damiano
Cellamare, Saverio
Catto, Marco
author_facet Bolognino, Isabella
Giangregorio, Nicola
Pisani, Leonardo
de Candia, Modesto
Purgatorio, Rosa
Tonazzi, Annamaria
Altomare, Cosimo Damiano
Cellamare, Saverio
Catto, Marco
author_sort Bolognino, Isabella
collection PubMed
description The orphan drug dantrolene (DAN) is the only therapeutic treatment for malignant hyperthermia (MH), a pharmacogenetic pathology affecting 0.2 over 10,000 people in the EU. It acts by inhibiting ryanodine receptors, which are responsible for calcium recruitment in striatal muscles and brain. Because of its involvement in calcium homeostasis, DAN has been successfully investigated for its potential as neuroprotecting small molecule in several animal models of Alzheimer’s disease (AD). Nevertheless, its effects at a molecular level, namely on putative targets involved in neurodegeneration, are still scarcely known. Herein, we present a prospective study on repurposing of DAN involving, besides the well-known calcium antagonism, inhibition of monoamine oxidase B and acetylcholinesterase, cytoprotection from oxidative insult, and activation of carnitine/acylcarnitine carrier, as concurring biological activities responsible for neuroprotection.
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spelling pubmed-69305242019-12-26 A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease Bolognino, Isabella Giangregorio, Nicola Pisani, Leonardo de Candia, Modesto Purgatorio, Rosa Tonazzi, Annamaria Altomare, Cosimo Damiano Cellamare, Saverio Catto, Marco Molecules Article The orphan drug dantrolene (DAN) is the only therapeutic treatment for malignant hyperthermia (MH), a pharmacogenetic pathology affecting 0.2 over 10,000 people in the EU. It acts by inhibiting ryanodine receptors, which are responsible for calcium recruitment in striatal muscles and brain. Because of its involvement in calcium homeostasis, DAN has been successfully investigated for its potential as neuroprotecting small molecule in several animal models of Alzheimer’s disease (AD). Nevertheless, its effects at a molecular level, namely on putative targets involved in neurodegeneration, are still scarcely known. Herein, we present a prospective study on repurposing of DAN involving, besides the well-known calcium antagonism, inhibition of monoamine oxidase B and acetylcholinesterase, cytoprotection from oxidative insult, and activation of carnitine/acylcarnitine carrier, as concurring biological activities responsible for neuroprotection. MDPI 2019-11-25 /pmc/articles/PMC6930524/ /pubmed/31775359 http://dx.doi.org/10.3390/molecules24234298 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bolognino, Isabella
Giangregorio, Nicola
Pisani, Leonardo
de Candia, Modesto
Purgatorio, Rosa
Tonazzi, Annamaria
Altomare, Cosimo Damiano
Cellamare, Saverio
Catto, Marco
A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease
title A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease
title_full A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease
title_fullStr A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease
title_full_unstemmed A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease
title_short A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease
title_sort prospective repurposing of dantrolene as a multitarget agent for alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930524/
https://www.ncbi.nlm.nih.gov/pubmed/31775359
http://dx.doi.org/10.3390/molecules24234298
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