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2004 Fiscal Year Final Research Report Summary

Molecular pathological analysis of citrullinated proteins in the brain from neurodegenerative disorder patients.

Research Project

Project/Area Number 14570210
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

ISHIGAMI Akihito  Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Research scientist, 福祉振興財団・東京都老人総合研究所, 研究員 (50270658)

Co-Investigator(Kenkyū-buntansha) MARUYAMA Naoki  Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Vice director, 福祉振興財団・東京都老人総合研究所, 副所長 (00115940)
HANDA Setsuko  Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Research assistant, 福祉振興財団・東京都老人総合研究所, 助手 (30360697)
Project Period (FY) 2002 – 2004
Keywordsneurodegenerative disorder / Alzheimer's disease / peptidylarginine deiminase / citrullinated protein / myelin basic protein / astrocyte / aging / proteome
Research Abstract

Citrullinated proteins are the products of a post-translational process in which arginine residues undergo modification into citrulline residues when catalyzed by peptidylarginine deiminases(PADs) in a calcium ion-dependent manner. Enzymatic citrullination abolishes positive charges of native protein molecules, inevitably causing significant alterations in their structure and functions. In mammalian tissues, PADs are found as five different isoforms (i.e, types 1-4,6). PAD2 expressed mainly in the rat cerebrum became activated early in the neurodegenerative process. To elucidate the involvement of the citrullination in neuronal degeneration, we examined whether citrullinated proteins are produced in Alzheimer's disease(AD), Parkinson's disease, and Huntington chorea.
1.Histochemical analysis revealed that citrullinated proteins were detected all over the hippocampus. However, no citrullinated proteins were detected in the normal hippocampus. PAD2 immunoreactivity was also detected all over the hippocampus both in the AD and the normal brain. Double immunofluorescence staining revealed that citrullinated protein- and PAD2-positive cells were well-coinddenced with GFAP-positive cells, but not all GFAP-positive cells were PAD2-positive cells. As GFAP is a astrocyte-spedfic marker protein, PAD2 is distributed mainly in astrocytes.
2.Citrullinated proteins with various molecular weight were detected in AD hippocampus by Western blot analysis, but not in normal brain. Two of the citrullinated proteins were identified as a vimentin and a glial fibrillary acidic protein(GFAP).
Thus, abnormal accumulation of citrullinated proteins and abnormal activation of PAD2 is occurring in AD hippocampus. These results strongly suggested that PAD has an important role in the onset and progression of AD and citrullinated proteins may became a possible useful marker for human neurodegenerative disease.

  • Research Products

    (10 results)

All 2005 2004 2003 2002

All Journal Article (10 results)

  • [Journal Article] Abnormal accumulation of deiminated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease.2005

    • Author(s)
      Ishigami, A., Ohsawa, T.et al.
    • Journal Title

      J.Neurosci.Res. 80

      Pages: 120-128

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Abnormal accumulation of deiminated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease.2005

    • Author(s)
      Ishigami, A., Ohsawa, T., Hiratsuka, M., Taguchi, H., Kobayashi, S., Saito, Y., Murayama, S., Asaga, H., Toda, T., Kimura, N., Maruyama, N.
    • Journal Title

      J.Neurosci.Res. 80

      Pages: 120-128

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] シトルリン化蛋白質と関節リウマチ2004

    • Author(s)
      石神昭人, 丸山直記
    • Journal Title

      医学のあゆみ 211

      Pages: 253-254

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] cDNA cloning, gene organization and expression analysis of human peptidylarginine deiminase type I2003

    • Author(s)
      Guerrin, M., Ishigami, A.et al.
    • Journal Title

      Biochem.J. 370

      Pages: 167-174

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] cDNA cloning, gene organization and expression analysis of human peptidylarginine deiminase type I.2003

    • Author(s)
      Guerrin, M., Ishigami, A., Mechin, MC., Nachat, R., Valmary, S., Sebbag, M., Simon, M., Senshu, T., Serre, G.
    • Journal Title

      Biochem.J. 370

      Pages: 167-174

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 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.2002

    • Author(s)
      Asaga, H., Akiyama, K., Ohsawa, T., Ishigami, A.
    • Journal Title

      Neurosci.Lett. 326

      Pages: 129-132

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Human peptidylarginine deiminase type II : Molecular cloning, gene organization and expression in human skin.2002

    • Author(s)
      Ishigami, A., Ohsawa, T.et al.
    • Journal Title

      Arch.Biochem.Biophys. 407

      Pages: 25-31

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Protein deimination and peptidylarginine deiminase expression during cornification of rat epidermal keratinocytes.2002

    • Author(s)
      Ishigami, A., Asaga, H., et al.
    • Journal Title

      Biomed.Res. 23

      Pages: 145-151

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Human peptidylarginine deiminase type II : Molecular cloning, gene organization and expression in human skin.2002

    • Author(s)
      Ishigami, A., Ohsawa, T., Asaga, H., Akiyama, K, Kuramoto, M., Maruyama, N.
    • Journal Title

      Arch.Biochem.Biophys. 407

      Pages: 25-31

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Protein deimination and peptidylarginine deiminase expression during cornification of rat epidermal keratinocytes.2002

    • Author(s)
      Ishigami, A., Asaga, H., Ohsawa, T., Akiyama, K., Maruyama, N.
    • Journal Title

      Biomed.Res. 23

      Pages: 145-151

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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