Allosteric Modulation of GSK-3ß as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related.
Int J Mol Sci
; 22(14)2021 Jul 08.
Article
in En
| MEDLINE
| ID: mdl-34298987
ABSTRACT
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 3ß (GSK-3ß), restore the expression and phosphorylation of these proteins in LGMDR1 cells, opening the possibility of their use as therapeutic options.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Muscular Dystrophies, Limb-Girdle
/
Glycogen Synthase Kinase 3 beta
/
Nerve Tissue Proteins
Language:
En
Journal:
Int J Mol Sci
Year:
2021
Document type:
Article
Affiliation country:
España