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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6930524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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