Dowling, Paul and Doran, Philip and Lohan, James and Culligan, Kevin and Ohlendieck, Kay
(2004)
Naturally Protected Muscle Phenotypes: Development of Novel
Treatment Strategies for Duchenne Muscular Dystrophy.
Basic and applied myology : BAM, 14 (3).
pp. 169-177.
ISSN 1120-9992
Abstract
Primary abnormalities in the dystrophin gene underlie x-linked muscular dystrophy.
However, the absence of the dystrophin isoform Dp427 does not necessarily result in a
severe dystrophic phenotype in all muscle groups. Distal mdx muscles, namely extraocular
and toe fibres, appear to represent a protected phenotype in muscular dystrophy. Thus, a
comparative analysis of affected versus naturally protected muscle cells should lead to a
greater knowledge of the molecular pathogenesis of inherited neuromuscular disorders.
Furthermore, rationalising the protective cellular mechanisms might help in developing
new treatment strategies for muscular dystrophy. The rescuing of extraocular and toe
muscle fibres has previously been attributed to the special protective properties of fasttwitching
small-diameter fibres. More recent biochemical studies have shown that the upregulation
of the autosomal dystrophin homologue named utrophin and the concomitant
rescue of dystrophin-associated glycoproteins also plays an important role in the
mechanical stabilisation of Dp427-deficient fibres. This result is mirrored in the dystrophic
mdx brain where the dystrophin isoform Dp71 seems to be responsible for the preservation
of the dystroglycan complex. It is envisaged that future proteomics-based comparisons of
naturally protective extraocular, toe and brain tissues with severely affected skeletal muscle
fibres will greatly add to our general understanding of the pathophysiology of muscular
dystrophy.
| Item Type: |
Article
|
| Keywords: |
Duchenne muscular dystrophy; Dystrophin; dystrophin-glycoprotein complex; dystroglycan; Dp427; Dp71; mdx; utrophin; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
7347 |
| Depositing User: |
Paul Dowling
|
| Date Deposited: |
16 Aug 2016 15:46 |
| Journal or Publication Title: |
Basic and applied myology : BAM |
| Publisher: |
Unipress |
| Refereed: |
Yes |
| Funders: |
Enterprise Ireland (EI), Health Research Board (HRB), Muscular Dystrophy Ireland, European Commission |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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