Muscle Weakness In Muscular Dystrophy Research Articles

Changes in cytosolic Ca2+dynamics associated with muscular dystrophy.

Duchenne muscular dystrophy(DMD)is X-linked genetic disorder caused by a lack of the membrane-associated protein dystrophin. DMD is characterized by progressive muscle wasting secondary to repeated muscle damage and inadequate repair. The mechanisms underlying the functional impairments in dystrophic muscle have not yet been fully determined. However, several recent studies indicate that elevated intracellular Ca2+homeostasis is a cause or facilitator of the development of muscle weakness in muscular dystrophy. This review focuses on abnormalities of Ca2+homeostasis and the possibilities for treatment by counteracting the Ca2+dysregulation.

S.P.54 The effects of ankle position to function in Duchenne muscular dystrophy

Abstract The progressive muscle weakness in muscular dystrophy causes muscle shortenings and joint limitations that effects the functions of children. The study was planned to investigate the effects of ankle limitation on functions in children with Duchenne Muscular Dystrophy. Fourty-three DMD patients (mean age 96.84 ± 28.08 months) who are in first and second level according to Brooke Scale were included to the study. Weight, height, hip, knee and ankle joint limitations, 10 m walking time, total lower extremity muscle strength (hip flexors, extansors, abductors and adductors, knee flexors and extansors, ankle dorsi and plantar flexors) and functional independence level according to WeeFIM (114,21 ± 13,97) of children were recorded. There were negavite correlations between ankle limitation and lower extremity muscle strength ( r = −0.381) and WeeFIM locomotion subtitle ( r = −0.358) ( p = 0.005). There were positive correlations between ankle limitation and height ( r = 0.575, p r = 0.577, p r = 0.475, p r = 0,368) and Brooke functional level ( r = 0.397, p

Mechanisms of muscle weakness in muscular dystrophy

Disruption of dystrophin or the sarcoglycans within the dystrophin protein complex leads to muscular dystrophy. The dystrophin complex is enriched in myofibers and concentrated into costameres, rib-like structures in the plasma membrane. In the absence of dystrophin, the plasma membrane becomes

Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness and early death resulting from dystrophin deficiency. Loss of dystrophin results in disruption of a large dystrophin glycoprotein complex (DGC) leading to pathologic calcium (Ca2+)-dependent signals that damage muscle cells 1–5. We have identified a structural and functional defect in the sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor (RyR1) in the mdx mouse model of muscular dystrophy that may contribute to altered Ca2+ homeostasis in dystrophic muscles. RyR1 isolated from mdx skeletal muscle exhibited an age-dependent increase in S-nitrosylation coincident with dystrophic changes in the muscle. RyR1 S-nitrosylation depleted the channel complex of FKBP12 (or “calstabin1” for calcium channel stabilizing binding protein) resulting in “leaky” channels. Preventing calstabin1 depletion from RyR1 using S107, a compound that binds to the RyR1 channel and enhances the binding affinity of calstabin1 to the nitrosylated channel, inhibited SR Ca2+ leak, reduced biochemical and histologic evidence of muscle damage, improved muscle function and increased exercise performance in mdx mice. Thus, SR Ca2+ leak via RyR1 due to S-nitrosylation of the channel and calstabin1 depletion likely contributes to muscle weakness in muscular dystrophy and preventing the RyR1-mediated SR Ca2+ leak may provide a novel therapeutic approach.

Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle

α-Dystrobrevin is a component of the dystrophin-glycoprotein complex (DGC) and is thought to have both structural and signaling roles in skeletal muscle. Mice deficient for α-dystrobrevin (adbn−/−) exhibit extensive myofiber degeneration and neuromuscular junction abnormalities. However, the biochemical stability of the DGC and the functional performance of adbn−/− muscle have not been characterized. Here we show that the biochemical association between dystrophin and β-dystroglycan is compromised in adbn−/− skeletal muscle, suggesting that α-dystrobrevin plays a structural role in stabilizing the DGC. However, despite muscle cell death and DGC destabilization, costamere organization and physiological performance is normal in adbn−/− skeletal muscle. Our results demonstrate that myofiber degeneration alone does not cause functional deficits and suggests that more complex pathological factors contribute to the development of muscle weakness in muscular dystrophy.