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    Mass Spectrometry-Based Identification of Muscle-Associated and Muscle-Derived Proteomic Biomarkers of Dystrophinopathies

    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

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    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:
    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
    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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