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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8308041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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