Allosteric modulation of GSK‐3β as a new therapeutic approach in limb girdle muscular dystrophy R1 Calpain 3‐related

Abstract

Limb‐girdle muscular dystrophy R1 calpain 3‐related (LGMDR1) is an autosomal reces-sive 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.