Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related
Autor: | Leire Casas-Fraile, Valle Palomo, Garazi Guembelzu, Anabel Rico, Ana Aiastui, Amets Sáenz, Adolfo López de Munain, Andrea Valls, Ana Martínez |
---|---|
Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Commission, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Instituto de Salud Carlos III, Asociación Guipuzcoana de Enfermos Neuromusculares, Eusko Jaurlaritza, Rico, Anabel [0000-0002-3002-6688], Palomo, Valle [0000-0002-1473-4086], Martínez, Ana [0000-0002-2707-8110], Casas-Fraile, Leire [0000-0002-7504-6578], Valls, Andrea [0000-0002-9211-4034], López de Munain, Adolfo [0000-0002-9509-4032], Sáenz, Amets [0000-0002-0704-1150], Rico, Anabel, Palomo, Valle, Martínez, Ana, Casas-Fraile, Leire, Valls, Andrea, López de Munain, Adolfo, Sáenz, Amets |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Muscle Fibers Skeletal Muscle Proteins Quinolones Adenosine Triphosphate 0302 clinical medicine CAPN3 GSK-3 VP0.7 Phosphorylation Muscular dystrophy Biology (General) Wnt Signaling Pathway Spectroscopy biology Calpain limb-girdle muscular dystrophy TOR Serine-Threonine Kinases Intracellular Signaling Peptides and Proteins Wnt signaling pathway General Medicine CD56 Antigen LGMDR1 Computer Science Applications Cell biology Chemistry Hydrazines mTOR Limb-girdle muscular dystrophy Allosteric Site Signal Transduction QH301-705.5 Nerve Tissue Proteins Article Catalysis Inorganic Chemistry tideglusib 03 medical and health sciences Wnt Thiadiazoles medicine Humans Physical and Theoretical Chemistry Molecular Biology QD1-999 PI3K/AKT/mTOR pathway Glycogen Synthase Kinase 3 beta business.industry GSK-3β Tideglusib Organic Chemistry Dystrophy Fibroblasts medicine.disease 030104 developmental biology Gene Expression Regulation Muscular Dystrophies Limb-Girdle biology.protein business Protein Processing Post-Translational Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery |
Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 14 International Journal of Molecular Sciences, Vol 22, Iss 7367, p 7367 (2021) Digital.CSIC. Repositorio Institucional del CSIC instname |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms22147367 |
Popis: | 18 p.-8 fig.-1 tab. 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 This work was financed through the grants received from the Health Research Fund (PI16/01325, PI17/01841 and DTS19/00061) of the Spanish Ministry of Economy and Competitiveness and the European Union (ERDF) and it was in part supported by the Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED: CB06/05/1126 to A.R., G.G., A.V., L.C.-F., A.L.d.M. and A.S. and CB18/05/00040 to A.M. and V.P.), Carlos III Health Institute and by GENE (Association of Neuromuscular diseases of Gipuzkoa). A.R. was supported by the predoctoral fellowship given by the department of Education, Universities and Research of the Basque Government (PRE-2016-1-0382). |
Databáze: | OpenAIRE |
Externí odkaz: |