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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
Defective glycosylation in muscular dystrophy
Francesco Muntoni1, Martin Brockington, Derek J Blake
1The Dubowitz Neuromuscular Centre, Department of Paediatrics, Imperial College London, Hammersmith Hospital Campus, W12 0NN, London, UK. f.muntoni@ic.ac.uk
Lancet (London, England)
|November 9, 2002
Summary
Aberrant glycosylation of alpha-dystroglycan causes muscular dystrophy and brain disorders. This finding shifts focus to protein modifications in disease pathogenesis, revealing new research avenues.
Area of Science:
- Molecular biology
- Genetics
- Neuroscience
Background:
- Inherited muscular dystrophies are linked to genes encoding muscle protein components.
- Post-translational protein modifications are increasingly implicated in muscular dystrophy pathogenesis.
- Aberrant glycosylation of alpha-dystroglycan is a common feature in recent muscular dystrophy discoveries.
Purpose of the Study:
- To investigate the role of aberrant glycosylation in muscular dystrophy.
- To explore the function of alpha-dystroglycan in muscle and brain development.
- To identify new therapeutic targets for muscular dystrophies and neuronal migration disorders.
Main Methods:
- Analysis of alpha-dystroglycan glycosylation in patients and mouse models.
- Assessment of extracellular matrix ligand binding to alpha-dystroglycan.
- Comparison of neuronal migration defects in affected mice and human patients.
Main Results:
- Patients with muscle-eye-brain disease and Fukuyama congenital muscular dystrophy exhibit abnormally glycosylated alpha-dystroglycan.
- Abnormally glycosylated alpha-dystroglycan fails to bind key extracellular matrix ligands.
- Similar neuronal migration disorders are observed in myodystrophy mice and alpha-dystroglycan knock-out models.
Conclusions:
- Alpha-dystroglycan plays a critical role in both muscle and brain development.
- Abnormal glycosylation of alpha-dystroglycan underlies certain muscular dystrophies and neuronal migration disorders.
- Further research into protein glycosylation may uncover causes for other uncharacterized genetic disorders.
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