Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor ne...

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Detalhes bibliográficos
Autores: Munk, Estefanía de, Palomo, Valle, Muñoz Sáez, Emma, Pérez, Daniel I., Gómez Miguel, Begoña, Solas Alados, Mª Teresa, Gil, Carmen, Martínez, Ana, Arahuetes Portero, Rosa María
Formato: artículo
Fecha de publicación:2016
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/17606
Acesso em linha:https://hdl.handle.net/20.500.14352/17606
Access Level:acceso abierto
Palavra-chave:591.1
612.8
Autophagic cell death
Spinal cord
Motor neuron diseases
Animal mode disease
Fisiología animal (Biología)
Neurociencias (Biológicas)
2401.13 Fisiología Animal
2490 Neurociencias
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oai_identifier_str oai:docta.ucm.es:20.500.14352/17606
network_acronym_str ES
network_name_str España
repository_id_str
spelling Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating AutophagyMunk, Estefanía dePalomo, ValleMuñoz Sáez, EmmaPérez, Daniel I.Gómez Miguel, BegoñaSolas Alados, Mª TeresaGil, CarmenMartínez, AnaArahuetes Portero, Rosa María591.1612.8Autophagic cell deathSpinal cordMotor neuron diseasesAnimal mode diseaseFisiología animal (Biología)Neurociencias (Biológicas)2401.13 Fisiología Animal2490 NeurocienciasAmyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor neuron disease animal model has been developed using β-Nmethylamino-L-alanine (L-BMAA), a neurotoxic amino acid related to the appearing of ALS. In the present work, the neuroprotective role of VP2.51, a small heterocyclic GSK-3 inhibitor, is analysed in this novel murine model together with the analysis of autophagy. VP2.51 daily administration for two weeks, starting the first day after L-BMAA treatment, leads to total recovery of neurological symptoms and prevents the activation of autophagic processes in rats. These results show that the L-BMAA murine model can be used to test the efficacy of new drugs. In addition, the results confirm the therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS.Public Library of Sciences (PLOS)Universidad Complutense de Madrid20162016-09-1520162016-09-15journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/17606reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/176062026-06-02T12:44:21Z
dc.title.none.fl_str_mv Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy
title Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy
spellingShingle Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy
Munk, Estefanía de
591.1
612.8
Autophagic cell death
Spinal cord
Motor neuron diseases
Animal mode disease
Fisiología animal (Biología)
Neurociencias (Biológicas)
2401.13 Fisiología Animal
2490 Neurociencias
title_short Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy
title_full Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy
title_fullStr Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy
title_full_unstemmed Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy
title_sort Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy
dc.creator.none.fl_str_mv Munk, Estefanía de
Palomo, Valle
Muñoz Sáez, Emma
Pérez, Daniel I.
Gómez Miguel, Begoña
Solas Alados, Mª Teresa
Gil, Carmen
Martínez, Ana
Arahuetes Portero, Rosa María
author Munk, Estefanía de
author_facet Munk, Estefanía de
Palomo, Valle
Muñoz Sáez, Emma
Pérez, Daniel I.
Gómez Miguel, Begoña
Solas Alados, Mª Teresa
Gil, Carmen
Martínez, Ana
Arahuetes Portero, Rosa María
author_role author
author2 Palomo, Valle
Muñoz Sáez, Emma
Pérez, Daniel I.
Gómez Miguel, Begoña
Solas Alados, Mª Teresa
Gil, Carmen
Martínez, Ana
Arahuetes Portero, Rosa María
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 591.1
612.8
Autophagic cell death
Spinal cord
Motor neuron diseases
Animal mode disease
Fisiología animal (Biología)
Neurociencias (Biológicas)
2401.13 Fisiología Animal
2490 Neurociencias
topic 591.1
612.8
Autophagic cell death
Spinal cord
Motor neuron diseases
Animal mode disease
Fisiología animal (Biología)
Neurociencias (Biológicas)
2401.13 Fisiología Animal
2490 Neurociencias
description Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor neuron disease animal model has been developed using β-Nmethylamino-L-alanine (L-BMAA), a neurotoxic amino acid related to the appearing of ALS. In the present work, the neuroprotective role of VP2.51, a small heterocyclic GSK-3 inhibitor, is analysed in this novel murine model together with the analysis of autophagy. VP2.51 daily administration for two weeks, starting the first day after L-BMAA treatment, leads to total recovery of neurological symptoms and prevents the activation of autophagic processes in rats. These results show that the L-BMAA murine model can be used to test the efficacy of new drugs. In addition, the results confirm the therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-09-15
2016
2016-09-15
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/17606
url https://hdl.handle.net/20.500.14352/17606
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Sciences (PLOS)
publisher.none.fl_str_mv Public Library of Sciences (PLOS)
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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