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
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