A Top-Down Proteomic Approach for Understanding Multiple Sclerosis — ASN Events
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  2. Symposium Four: Students of APS (SoAPS)
  3. A Top-Down Proteomic Approach for Understanding Multiple Sclerosis

A Top-Down Proteomic Approach for Understanding Multiple Sclerosis (#13)

Melissa A Partridge 1 2 , Simon J Myers 2 3 , Sumana Gopinath 2 4 , Jens R Coorssen 1 2
  1. Department of Molecular Physiology, School of Medicine, University of Western Sydney, Penrith, NSW, Australia
  2. Molecular Medicine Research Group, School of Medicine, University of Western Sydney, Penrith, NSW, Australia
  3. Neuro-Cell Biology Laboratory, School of Science and Health, University of Western Sydney, Penrith, NSW, Australia
  4. Department of Neurology, Campbelltown Hospital, Campbelltown, NSW, Australia

Multiple Sclerosis (MS) is conventionally thought to be initiated by an autoimmune T cell response. However, there is an alternate hypothesis that MS may begin as a slow, progressive (i.e. clinically undetected) degeneration of oligodendrocytes [1-3]. Currently the molecular mechanism(s) behind such a degeneration are poorly understood. To address this we have initiated a systems-wide analysis of an animal model of oligodendrocyte degeneration: the cuprizone model. We have undertaken a top-down analytical approach to investigate the breadth of proteomic alterations that cuprizone treatment has on the cortex, skeletal muscle, spleen, and peripheral blood mononuclear cells. Using 2-dimensional gel electrophoresis, deep imaging, and mass spectrometry we have identified 43 protein species as uniquely present or absent in the cuprizone treatment group. Protein species identified in the cortex are potentially linked to primary oligodendrocyte degeneration and secondary axonal damage. Furthermore, we identified alterations in the proteomes of skeletal muscle, spleen, and peripheral blood mononuclear cells following cuprizone treatment; arginase-1 was a notable hit in the spleen and has previously been linked to T cell suppression in an animal autoimmune model of MS [4-6]. A further notable finding was the absence of protein disulphide isomerase subunits in the spleen and peripheral blood mononuclear cells of the cuprizone treatment group; this may further contribute to impaired MHC class I assembly leading to reduced antigen presentation and potentially contributing to the lack of T cell response in this model [7]. Overall, the results of this study suggest that findings from the cuprizone model and likely others need to be carefully considered relative to clinical MS.

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  7. Kang, K., Park, B., Oh, C., Cho, K., Ahn, K., A role for protein disulfide isomerase in the early folding and assembly of MHC class I molecules. Antioxidants & redox signaling 2009, 11, 2553-2561.