Журнал гликомики и липидомики
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Molecular pathogenesis of motor neuron disease as revealed by mass spectrometry-based proteomics

Kay Ohlendieck

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