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Identification and characterisation of novel marker proteins involved in X-linked muscular dystrophy


Progressive X-linked muscular dystrophy represents the most commonly inherited
neuromuscular disorder in humans. Although the primary abnormality lies with the loss
of dystrophin and reduction of its associated glycoprotein complex, secondary
alterations in metabolic pathways, cellular signalling and ion homeostasis regulation
cause fibre degeneration leading to severe muscle weakness. Skeletal muscle
deteriorates to the extent that sufferers are wheelchair bound by early adulthood and
severe diaphragm degeneration can lead to respiratory failure. Therapy in this area has
lengthened life-span but at a more advanced stage of the disease, most Duchenne
muscular dystrophy patients suffer cardiomyopathic complications.
The purpose of this study was to carry out proteomic profiling on differentially affected
dystrophic tissues. Differences in protein concentration levels of the severely affected
cardiac muscle and the naturally protected extraocular muscle were used to explore
pathogenesis of the disease.
A mass spectrometry-based approach combined with the highly sensitive difference
in-gel electrophoresis technique was used to reveal changes and identify novel
biomarkers in the dystrophic tissues. Following the pathogenesis of the disease the
naturally protected tissue displayed only moderate changes in protein concentration
expression. With a replacement of dystrophin with its homologue utrophin, restoration
of β-dystroglycan was observed along with an increased concentration in heat shock
proteins. While the severely affected cardiac muscle exhibited drastic decreases in the
expression levels of many proteins involved in energy metabolism including adenylate
kinase and many ATP synthase isoforms. Reduced concentrations were also observed
in numerous contractile proteins and intermediate filament proteins. With the loss of
these structural elements, a drastic increase in stress proteins was observed within
dystrophic myofibrils compared to normal fibres.
This thesis has successfully identified novel biomarkers that may be used to
determine suitability of new treatments or therapies of muscular dystrophy.



Suggested citation:

. () Identification and characterisation of novel marker proteins involved in X-linked muscular dystrophy [Online]. Available from: [Accessed: 16th June 2019].


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