Journal Article

Calcium Mechanisms in Limb-Girdle Muscular Dystrophy with CAPN3 Mutations

Lasa-Elgarresta, Jaione, Mosqueira-Martín, Laura, Naldaiz-Gastesi, Neia, López de Munain, Adolfo, Vallejo-Illarramendi, Ainara, Sáenz, Amets

2019

Overview

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), previously known as LGMD2A, is a rare disease caused by mutations in the CAPN3 gene. It is characterized by progressive weakness of shoulder, pelvic, and proximal limb muscles that usually appears in children and young adults and results in loss of ambulation within 20 years after disease onset in most patients. The pathophysiological mechanisms involved in LGMDR1 remain mostly unknown, and to date, there is no effective treatment for this disease. Here, we review clinical and experimental evidence suggesting that dysregulation of Ca2+ homeostasis in the skeletal muscle is a significant underlying event in this muscular dystrophy. We also review and discuss specific clinical features of LGMDR1, CAPN3 functions, novel putative targets for therapeutic strategies, and current approaches aiming to treat LGMDR1. These novel approaches may be clinically relevant not only for LGMDR1 but also for other muscular dystrophies with secondary calpainopathy or with abnormal Ca2+ homeostasis, such as LGMD2B/LGMDR2 or sporadic inclusion body myositis.

• Publisher: MDPI AG,MDPI
• Subject: Biosynthesis / Calcium - metabolism / Calcium Signaling / Calpain - genetics / Cell growth / Gene expression / Genotype & phenotype / Homeostasis / Humans / Kinases / Metabolism / Mitochondria / Motility / Muscle contraction / Muscle Proteins - genetics / Muscle, Skeletal - metabolism / Muscular Dystrophies, Limb-Girdle - genetics / Muscular Dystrophies, Limb-Girdle - metabolism / Muscular dystrophy / Musculoskeletal system / Mutation / Phosphorylation / Proteins / Review / Sensors