Decreased calcineurin activity in circulation of Duchenne muscular dystrophy

Sundaram, Jagannathan; Rao, V. Mohana; Meena, A K; Anandaraj, M.P.J.S.

doi:10.1016/j.clinbiochem.2007.01.006

Cited by 11 publications

(10 citation statements)

References 22 publications

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“…Conversely, transgenic overexpression of a small peptide inhibitor for calmodulin, an upstream activator of calcineurin, represses the levels of utrophin, and exacerbates dystrophic phenotype in mdx slow-type fibers (Chakkalakal et al, 2006). It is notable that in comparison to mdx mice, serum level of calcineurin is significantly lower in DMD patients (Sundaram et al, 2007) which may account for the impairment of muscle regeneration, insufficient utrophin expression, and severe pathology in DMD patients. While published reports indicate stimulation of calcineurin/NFAT pathway as a promising therapy for DMD, the potential of negative side-effects caused by activation of calcineurin-NFAT signaling in other tissues must not be overlooked.…”

Section: Membrane Instability and Calcium Influxmentioning

confidence: 99%

Wasting mechanisms in muscular dystrophy

Shin

Tajrishi

Ogura

et al. 2013

The International Journal of Biochemistry & Cell Biology

122

138

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Muscular dystrophy is a group of more than 30 different clinical genetic disorders that are characterized by progressive skeletal muscle wasting and degeneration. Primary deficiency of specific extracellular matrix, sarcoplasmic, cytoskeletal, or nuclear membrane protein results in several secondary changes such as sarcolemmal instability, calcium influx, fiber necrosis, oxidative stress, inflammatory response, breakdown of extracellular matrix, and eventually fibrosis which leads to loss of ambulance and cardiac and respiratory failure. A number of molecular processes have now been identified which hasten disease progression in human patients and animal models of muscular dystrophy. Accumulating evidence further suggests that aberrant activation of several signaling pathways aggravate pathological cascades in dystrophic muscle. Although replacement of defective gene with wild-type is paramount to cure, management of secondary pathological changes has enormous potential to improving the quality of life and extending lifespan of muscular dystrophy patients. In this article, we have reviewed major cellular and molecular mechanisms leading to muscle wasting in muscular dystrophy.

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Section: Membrane Instability and Calcium Influxmentioning

confidence: 99%

Wasting mechanisms in muscular dystrophy

Shin

Tajrishi

Ogura

et al. 2013

The International Journal of Biochemistry & Cell Biology

122

138

View full text Add to dashboard Cite

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“…It is also of interest to note that in comparison to mdx mice, serum level of calcineurin is significantly lower in DMD patients (94) which may account for the impairment of muscle regeneration, insufficient utrophin expression, and severe pathology in DMD patients.…”

Section: Calcineurin (Cn)/nfat In Muscular Dystrophymentioning

confidence: 99%

Therapeutic targeting of signaling pathways in muscular dystrophy

Bhatnagar

Kumar

2009

J Mol Med

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Muscular dystrophy refers to a group of genetic diseases that cause severe muscle weakness and loss of skeletal muscle mass. Although research has helped understanding the molecular basis of muscular dystrophy, there is still no cure for this devastating disorder. Numerous lines of investigation suggest that the primary deficiency of specific proteins causes aberrant activation of several cell signaling pathways in skeletal and cardiac muscle leading to the pathogenesis of muscular dystrophy. Studies using genetic mouse models and pharmacological approaches have provided strong evidence that the modulation of the activity of specific cell signaling pathways has enormous potential to improving the quality of life and extending the life expectancy in muscular dystrophy patients. In this article, we have outlined the current understanding regarding the role of different cell signaling pathways in disease progression with particular reference to different models of muscular dystrophy and the development of therapy.

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“…[17][18][19][20] Additionally, it has been demonstrated in humans that there is significantly reduced calcineurin levels in the serum of patients with Duchenne muscular dystrophy compared with controls. 21 Along with an important role in skeletal muscle differentiation, 22 the data above seem to suggest a protective and regenerative role of calcineurin in certain conditions. In contrast, there are certain pathological states for which calcineurin appears to have detrimental effects upon myocyte integrity and function.…”

Section: Discussionmentioning

confidence: 91%

Prevention of Recurrent Episodes of Rhabdomyolysis With Tacrolimus in a Transplant Recipient With Myopathy

Sathyan

Baskharoun

Perlman

2014

American Journal of Therapeutics

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Genetic muscular disorders are known risk factors for rhabdomyolysis, which may result in acute kidney injury. Recurrent episodes of acute kidney injury can lead to chronic kidney disease and eventually end-stage renal failure. We describe a patient with chronic kidney disease that developed in the setting of recurrent rhabdomyolysis, resulting in the requirement for renal transplantation. After transplantation, the maintenance of tacrolimus trough concentrations above what is typically prescribed for standard renal transplant recipients appeared to confer protection from further episodes of rhabdomyolysis. This is consistent with previous case series that demonstrated a therapeutic benefit of the calcineurin inhibitor cyclosporine in collagen VI myopathies in the nontransplant population. This case report suggests the potential application of higher tacrolimus targets in patients who have undergone renal transplantation in the setting of recurrent rhabdomyolysis leading to end-stage renal failure.

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Decreased calcineurin activity in circulation of Duchenne muscular dystrophy

Cited by 11 publications

References 22 publications

Wasting mechanisms in muscular dystrophy

Wasting mechanisms in muscular dystrophy

Therapeutic targeting of signaling pathways in muscular dystrophy

Prevention of Recurrent Episodes of Rhabdomyolysis With Tacrolimus in a Transplant Recipient With Myopathy

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