Molecular Pathogenesis Of Motor Neuron Disease As Revealed By Mass Spectrometry-based Proteomics | 28247
Journal of Clinical & Experimental Pathology
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The heterogeneous group of neurodegenerative syndromes that encapsulates motor neuron diseases is inherited or
spontaneous disorders that are associated with progressive muscular atrophy. Our laboratory has initiated a proteomic
profiling initiative to identify novel muscle-associated biomarkers of motor neuron disease using the wobbler mouse model
of primary motor neuronopathy. We employed two complementary methods, fluorescence two-dimensional difference ingel
electrophoresis and liquid chromatography in combination with label-free mass spectrometry. The proteomic analysis of
disease-induced muscular atrophy has revealed highly complex alterations in the abundance or isoform expression pattern
of a large number of skeletal muscle proteins involved in cellular signaling, excitation-contraction coupling, the cytoskeletal
network, ion homeostasis, energy metabolism and the cellular stress response. Interestingly, the complex changes in the muscle
proteome due to the progressive degeneration of individual motor neurons appears to be considerably different to the more
unilateral skeletal muscle transformation observed in disuse-associated muscular atrophy or denervated muscle fibers. Hence,
a subtype-specific vulnerability of neuromuscular synapses and compensatory mechanisms of fiber type shifting seem to exist
in motor neuron disease as compared to other forms of muscular atrophy. The newly identifiedproteomic biomarker candidates
of motor neuron disease may be useful for improving diagnostic, prognostic and therapeutic approaches.
Kay Ohlendieck has an undergraduate degree in Biology from the University of Konstanz, Germany (1985), a PhD in Biochemistry from University College Cork,
Ireland (1989) and a DSc in Muscle Biology from University College Dublin, Ireland (2011). He has worked as a Postdoctoral Associate at the University of Iowa,
Iowa City and at the State University of New York, Stony Brook, as well as a Lecturer in the Department of Pharmacology, University College Dublin (1995-2001).
Since 2002, he is Chair of Biology at the National University of Ireland, Maynooth, and his research focuses on skeletal muscle proteomics.
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