Localisation of citrullinated proteins in normal appearing white matter and lesions in the central nervous system in multiple sclerosis

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Bradford, Claire M. ; Ramos, Inês ; Cross, Alison K. ; Haddock, Gail ; McQuaid, Stephen ; Nicholas, Anthony P. ; Woodroofe, M. Nicola (2014)
  • Publisher: Elsevier BV
  • Journal: Journal of Neuroimmunology, volume 273, issue 1-2, pages 85-95 (issn: 0165-5728)
  • Related identifiers: doi: 10.1016/j.jneuroim.2014.05.007
  • Subject: Clinical Neurology | Immunology and Allergy | Immunology | Neurology

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, considered to be autoimmune in origin. Post-translational modification of central nervous system proteins, including glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP), through citrullination of arginine residues, may lead to exposure of neoepitopes, triggering autoimmunity. Here we investigated the expression of citrullinated proteins in active MS lesions, MS normal appearing white matter and control brain white matter. We demonstrate increased citrullinated GFAP and MBP by immunohistochemistry and western blotting in areas of ongoing demyelination, suggesting a pivotal role for deimination of GFAP and MBP in MS pathogenesis MS.
  • References (56)
    56 references, page 1 of 6

    Acharya, N.K., Nagele, E.P., Han, M., Coretti, N.J., DeMarshall, C., Kosciuk, M.C., Boulos, P.A., Nagele, R.G., 2012. Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease. J. Autoimmun. 38, 369-380.

    Akiyama, K., Inoue, K., Senshu, T., 1990. Immunocytochemical demonstration of skeletal muscle type peptidylarginine deiminase in various rat tissues. Cell Biol. Int. Rep. 14, 267-273.

    Asaga, H., Ishigami, A., 2000. Protein deimination in the rat brain: generation of citrullinecontaining proteins in cerebrum perfused with oxygen-deprived media. Biomed. Res. Tokyo 21, 197-206.

    Asaga, H., Ishigami, A., 2007. Microglial expression of peptidylarginine deiminase 2 in the prenatal rat brain. Cell. Mol. Biol. Lett. 12, 536-544.

    Asaga, H., Senshu, T., 1993. Combined biochemical and immunocytochemical analyses of postmortem protein deimination in the rat spinal cord. Cell Biol. Int. 17, 525-532.

    Asaga, H., Nakashima, K., Senshu, T., Ishigami, A., Yamada, M., 2001. Immunocytochemical localization of peptidylarginine deiminase in human eosinophils and neutrophils. J. Leukoc. Biol. 70, 46-51.

    Asaga, H., Akiyama, K., Ohsawa, T., Ishigami, A., 2002. Increased and type II-specific expression of peptidylarginine deiminase in activated microglia but not hyperplastic astrocytes following kainic acid-evoked neurodegeneration in the rat brain. Neurosci. Lett. 326, 129-132.

    Bak, L.K., Schousboe, A., Waagepetersen, H.S., 2006. The glutamate/GABA‐glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J. Neurochem. 98, 641-653.

    Beniac, D.R., Wood, D.D., Palaniyar, N., Ottensmeyer, F.P., Moscarello, M.A., Harauz, G., 2000. Cryoelectron microscopy of protein-lipid complexes of human myelin basic protein charge isomers differing in degree of citrullination. J. Struct. Biol. 129, 80-95.

    Boggs, J., 2006. Myelin basic protein: a multifunctional protein. Cell. Mol. Life Sci. 63, 1945-1961.

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