Dowling, Paul and Holland, Ashling and Ohlendieck, Kay
(2014)
Mass Spectrometry-Based Identification of
Muscle-Associated and Muscle-Derived
Proteomic Biomarkers of Dystrophinopathies.
Journal of Neuromuscular Diseases, 1 (1).
pp. 15-40.
ISSN 2214-3599
Abstract
The optimization of large-scale screening procedures of pathological specimens by genomic, proteomic and metabolic
methods has drastically increased the bioanalytical capability for swiftly identifying novel biomarkers of inherited disorders,
such as neuromuscular diseases. X-linked muscular dystrophy represents the most frequently inherited muscle disease and is
characterized by primary abnormalities in the membrane cytoskeletal protein dystrophin. Mass spectrometry-based proteomics
has been widely employed for the systematic analysis of dystrophin-deficient muscle tissues, using patient samples and animal
models of dystrophinopathy. Both, gel-based methods and label-free mass spectrometric techniques have been applied in comparative
analyses and established a large number of altered proteins that are associated with muscle contraction, energy metabolism,
ion homeostasis, cellular signaling, the cytoskeleton, the extracellular matrix and the cellular stress response. Although these new
indicators of muscular dystrophy have increased our general understanding of the molecular pathogenesis of dystrophinopathy,
their application as new diagnostic or prognostic biomarkers would require the undesirable usage of invasive methodology.
Hence, to reduce the need for diagnostic muscle biopsy procedures, more recent efforts have focused on the proteomic screening
of suitable body fluids, such as plasma, serum or urine, for the identification of changed concentration levels of muscle-derived
peptides, protein fragments or intact proteins. The occurrence of muscular dystrophy-related protein species in biofluids will
be extremely helpful for the future development of cost-effective and non-invasive diagnostic procedures. Novel biomarker
signatures of dystrophinopathies will be indispensible for the swift evaluation of innovative therapeutic approaches, such as
exon skipping, codon-read-through or stem cell therapy.
| Item Type: |
Article
|
| Additional Information: |
© 2014 – IOS Press and the authors. All rights reserved
This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License. Research in the author’s laboratory was supported
by project grants from Muscular Dystrophy Ireland
and the Irish Higher Education Authority (BioAT programme
of PRTLI cycle 5). |
| Keywords: |
Biomarker discovery; Duchenne muscular dystrophy; dystrophin; dystrophinopathy; mass spectrometry; muscle
pathology; neuromuscular disease; proteomics; skeletal muscle proteome; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
5633 |
| Identification Number: |
https://doi.org/10.3233/JND-140011 |
| Depositing User: |
Paul Dowling
|
| Date Deposited: |
18 Dec 2014 15:19 |
| Journal or Publication Title: |
Journal of Neuromuscular Diseases |
| Publisher: |
IOS Press |
| Refereed: |
Yes |
| Funders: |
Higher Education Authority |
| 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 |
Repository Staff Only(login required)
 |
Item control page |
Downloads per month over past year
Origin of downloads
Altmetric
Altmetric