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Deimination in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

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Protein Deimination in Human Health and Disease

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterised by focal areas of myelin loss, accompanied by inflammatory cell infiltrates, predominantly T cells and monocytes and microglial activation. Subsequent axonal damage leads to symptoms such as visual disturbance, sensory and motor impairment, pain and fatigue. Myelin basic protein (MBP), an essential component of myelin, is known to undergo post-translational modifications including citrullination which in in vitro studies lead to a more open molecular structure and an increased susceptibility to enzyme degradation. Citrullination of MBP may also generate new immunogenic epitopes. Excess citrullination has previously been reported in the CNS in post-mortem MS brain tissue with 45 % of MBP citrullinated in MS patients compared with 18 % in control tissue. Glial fibrillary acidic protein (GFAP), an astrocytic intermediate filament protein, has also been shown to be citrullinated in MS tissue and in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). This citrullination is carried out by peptidylarginine deiminase (PAD) enzymes of which PAD 2 and 4 are found in the brain. Studies on EAE have shown increased citrullinated proteins in diseased animals co-localising with GFAP and MBP, correlating with increased disease severity. Here we summarise the current literature on citrullination in MS and EAE and our own findings in relation to disease pathogenesis.

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Authors and Affiliations

  1. Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK

    Claire Bradford

  2. Department of Neurology, Birmingham Veterans Administration Medical Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Anthony P. Nicholas

  3. Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK

    Nicola Woodroofe & Alison K. Cross

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  1. Claire Bradford
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  4. Alison K. Cross
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Correspondence to Alison K. Cross .

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Editors and Affiliations

  1. Department of Neurology, University of Alabama at Birmingham and The Birmingham Veterans Administration Medical Center, Birmingham, Alabama, USA

    Anthony P. Nicholas

  2. Bascom Palmer Eye Institute, University of Miami, MIAMI, Florida, USA

    Sanjoy K. Bhattacharya

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© 2014 Springer Science+Business Media New York

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Bradford, C., Nicholas, A.P., Woodroofe, N., Cross, A.K. (2014). Deimination in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. In: Nicholas, A., Bhattacharya, S. (eds) Protein Deimination in Human Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8317-5_10

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