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Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related

Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy produced by mutations in the CAPN3 gene. It is a rare disease and there is no cure or treatment for the disease while the pathophysiological mechanism by which the absence of calpain 3 provokes...

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Autores principales: Rico, Anabel, Guembelzu, Garazi, Palomo, Valle, Martínez, Ana, Aiastui, Ana, Casas-Fraile, Leire, Valls, Andrea, López de Munain, Adolfo, Sáenz, Amets
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308041/
https://www.ncbi.nlm.nih.gov/pubmed/34298987
http://dx.doi.org/10.3390/ijms22147367
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author Rico, Anabel
Guembelzu, Garazi
Palomo, Valle
Martínez, Ana
Aiastui, Ana
Casas-Fraile, Leire
Valls, Andrea
López de Munain, Adolfo
Sáenz, Amets
author_facet Rico, Anabel
Guembelzu, Garazi
Palomo, Valle
Martínez, Ana
Aiastui, Ana
Casas-Fraile, Leire
Valls, Andrea
López de Munain, Adolfo
Sáenz, Amets
author_sort Rico, Anabel
collection PubMed
description Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy produced by mutations in the CAPN3 gene. It is a rare disease and there is no cure or treatment for the disease while the pathophysiological mechanism by which the absence of calpain 3 provokes the dystrophy in muscles is not clear. However, key proteins implicated in Wnt and mTOR signaling pathways, which regulate muscle homeostasis, showed a considerable reduction in their expression and in their phosphorylation in LGMDR1 patients’ muscles. Finally, the administration of tideglusib and VP0.7, ATP non-competitive inhibitors of glycogen synthase kinase 3β (GSK-3β), restore the expression and phosphorylation of these proteins in LGMDR1 cells, opening the possibility of their use as therapeutic options.
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spelling pubmed-83080412021-07-25 Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related Rico, Anabel Guembelzu, Garazi Palomo, Valle Martínez, Ana Aiastui, Ana Casas-Fraile, Leire Valls, Andrea López de Munain, Adolfo Sáenz, Amets Int J Mol Sci Article Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy produced by mutations in the CAPN3 gene. It is a rare disease and there is no cure or treatment for the disease while the pathophysiological mechanism by which the absence of calpain 3 provokes the dystrophy in muscles is not clear. However, key proteins implicated in Wnt and mTOR signaling pathways, which regulate muscle homeostasis, showed a considerable reduction in their expression and in their phosphorylation in LGMDR1 patients’ muscles. Finally, the administration of tideglusib and VP0.7, ATP non-competitive inhibitors of glycogen synthase kinase 3β (GSK-3β), restore the expression and phosphorylation of these proteins in LGMDR1 cells, opening the possibility of their use as therapeutic options. MDPI 2021-07-08 /pmc/articles/PMC8308041/ /pubmed/34298987 http://dx.doi.org/10.3390/ijms22147367 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rico, Anabel
Guembelzu, Garazi
Palomo, Valle
Martínez, Ana
Aiastui, Ana
Casas-Fraile, Leire
Valls, Andrea
López de Munain, Adolfo
Sáenz, Amets
Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related
title Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related
title_full Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related
title_fullStr Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related
title_full_unstemmed Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related
title_short Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related
title_sort allosteric modulation of gsk-3β as a new therapeutic approach in limb girdle muscular dystrophy r1 calpain 3-related
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308041/
https://www.ncbi.nlm.nih.gov/pubmed/34298987
http://dx.doi.org/10.3390/ijms22147367
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