Holland, Ashling and Schmitt-John, Thomas and Dowling, Paul and Meleady, Paula and Henry, Michael and Clynes, Martin and Ohlendieck, Kay (2014) Intricate effects of primary motor neuronopathy on contractile proteins and metabolic muscle enzymes as revealed by label-free mass spectrometry. Bioscience Reports, 34 (4). pp. 331-343. ISSN 1573-4935

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Abstract

While the long-term physiological adaptation of the neuromuscular system to changed functional demands is usually reflected by unilateral skeletal muscle transitions, the progressive degeneration of distinct motor neuron populations is often associated with more complex changes in the abundance and/or isoform expression pattern of contractile proteins and metabolic enzymes. In order to evaluate these intricate effects of primary motor neuronopathy on the skeletal muscle proteome, label-free MS was employed to study global alterations in the WR (wobbler) mouse model of progressive neurodegeneration. In motor neuron disease, fibre-type specification and the metabolic weighting of bioenergetic pathways appear to be strongly influenced by both a differing degree of a subtype-specific vulnerability of neuromuscular synapses and compensatory mechanisms of fibre-type shifting. Proteomic profiling confirmed this pathobiochemical complexity of disease-induced changes and showed distinct alterations in 72 protein species, including a variety of fibre-type-specific isoforms of contractile proteins, metabolic enzymes, metabolite transporters and ion-regulatory proteins, as well as changes in molecular chaperones and various structural proteins. Increases in slow myosin light chains and the troponin complex and a decrease in fast MBP (myosin-binding protein) probably reflect the initial preferential loss of the fast type of neuromuscular synapses in motor neuron disease.

Item Type:	Article
Additional Information:	©2014 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. The original article is available at Holland, A., Schmitt-John, T., Dowling, P., Meleady, P., Henry, M., Clynes, M. and Ohlendieck, K. (2014) Intricate effects of primary motor neuronopathy on contractile proteins and metabolic muscle enzymes as revealed by label-free mass spectrometry. Biosci. Rep. 34(4), art:e00119.doi:10.1042/BSR20140029 . This work was supported by the BioAT programme of the Irish Higher Education Authority (HEA PRTLI cycle 5). The Irish Higher Education Authority supported a laboratory visit of the Maynooth team in Denmark.
Keywords:	amyotrophic lateral sclerosis; motor neuron disease; muscle proteomics; muscular atrophy; skeletal muscle proteome; wobbler mouse;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	5632
Identification Number:	https://doi.org/10.1042/BSR20140029
Depositing User:	Paul Dowling
Date Deposited:	18 Dec 2014 15:19
Journal or Publication Title:	Bioscience Reports
Publisher:	Portland Press Ltd
Refereed:	Yes
Funders:	Higher Education Authority
URI:	http://www.bioscirep.org/bsr/default.htm
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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