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Analysis of the function of human brain carboxypeptidase B and its diagnostic significance in dementia of Alzheimer's type

Research Project

Project/Area Number 19591027
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionHimeji Dokkyo University

Principal Investigator

MATSUMOTO Akira  Himeji Dokkyo University, 薬学部, 客員教授 (80181759)

Co-Investigator(Kenkyū-buntansha) MATSUYAMA Shogo  姫路獨協大学, 薬学部, 教授 (80243319)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアルツマイマー病 / 軽度認知機能障害 / カルボキシペプチダーゼB / 立体構造認識 / モノクロナル抗体 / ベータアミロイド / CPB結合蛋白 / 結合ポケット / バイマーカー / エピトープ解析 / 立体構造 / 酵素 / 神経科学 / 痴呆 / トランスレーショナルリサーチ / 脳神経疾患
Research Abstract

1. Biochemical and in silico analyses of the CPB-BP binding pocket of human brain carboxypeptidase B (HBCPB) : In an attempt to understand the mechanism of action of HBCPB and its specific binding protein, CPB-BP (1 & 2), we have started an epitope mapping analyses by using antibodies generated based upon primary structures of the both proteins. These monoclonal antibodies (6 clones) exhibit sufficient specificity and sensitivity, and analyses of binding to CPB-BP (1 & 2) and its regulation have enabled classification of these in terms of difference in three-dimensional structures, apart from specificity and sensitivity. This achievement embodies a basis for structural analysis of the binding pocket and SBDD in the next experimental program.
2. A search and analysis for CPB-BP and related proteins in human serum. To facilitate HTP analyses for this purpose, the surface plasmon interaction analysis in combination with MALDI- TOF-MS was utilized. Using a peptide ligand corresponding to the C-terminal epitope of CPB, human peripheral serum samples, from which major abundant proteins were removed, were analyzed. In addition to the successful identification molecules previously determined by immunoprecipitation, a new molecule was identified, with which an interaction to the candidate molecule is recognized.
3. Immunohistochemical analyses of pathological specimen. All AD brain samples and a portion of brain samples from the normal aged both exhibit CPB-BP2 immunoreactivity in the hippocampus.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (10 results)

All 2009 2008 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (2 results)

  • [Journal Article] Quantitative analysis of beta-amyloid peptides expressed in human cerebrospinal fluid by an improved method of antibody-assisted time-of-flight mass spectrometry2009

    • Author(s)
      Akira Matsumoto, Reiko Matsumoto, Keiichi Kadoyama, Shogo Matsuyama, et al. (6名中1番目)
    • Journal Title

      International Journal of Peptide Research and Therapeutics 15

      Pages: 205-210

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Use of a phosphosensor dye in proteomic analysis of human mutant tau transgenic mouse2009

    • Author(s)
      Takano Masaoki, Otani Mieko, Shogo Matsuyama, Akira Matsumoto, et al. (9名中6番目)
    • Journal Title

      Neuro-report 20

      Pages: 1648-1653

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of β-amyloid peptides expressed in human cerebrospinal fluid by an improved method of antibody-assisted time-of-flight mass spectrometry.2009

    • Author(s)
      Akira Matsumoto, Reiko Matsumoto, Kei-ichi Kadoyama, Taka-aki Nishimoto, Shogo Matsuyama, Osamu Midorikawa
    • Journal Title

      International Journal of Peptide Research and Therapeutics 15

      Pages: 205-210

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Use of a phosphosensor dye in proteomic analysis of human mutant tau transgenic mouse.2009

    • Author(s)
      Takano Masaoki, Otani Mieko, Sakai Akiko,, Kei-ichi Kadoyama, Shogo Matsuyama, Akira Matsumoto, Mariko Takenokuchi, Miho Sumida, Taizo Taniguchi
    • Journal Title

      Neuroreport 20

      Pages: 1648-1653

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of beta-amyloid peptides expressed in human cerebrospinal fluid by an improved method of antibodv-assisted time-of-flight mass spectrometrv.2009

    • Author(s)
      Matsumoto A, et al.
    • Journal Title

      International Journal of Peptide Research and Theraoeutics 15(電子媒体掲載中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term potentiation-like facilicutation through GABA-A receptor blockage in the mouse dentate gyrus in vivo2008

    • Author(s)
      Shogo Matsuyama, Akira Matsumoto, et al. (4名中4番目)
    • Journal Title

      19

      Pages: 1809-1813

    • Related Report
      2009 Final Research Report
  • [Journal Article] Long-term potentiation-like facilitation through GABA-Areceptor blockage in the mouse dentate gyrus in vivo/2008

    • Author(s)
      Matsuyama S, et al.
    • Journal Title

      Neuroreport 19

      Pages: 1809-1813

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantiative analysis of beta-amyloid petides expressed in human cerebrospinal fluid by an improved method of antibody-assisted time-of-flight mass spectrometry

    • Author(s)
      Matsumoto, A., et. al.
    • Journal Title

      Int.J.Peptide Res (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Parkinsonism induced by tauopathy: analysis of SJLB mice2009

    • Author(s)
      Taizo Taniguchi, Akira Matsumoto, Shogo Matsuyama, et al
    • Organizer
      The 2009 ISN/APSN joint meeting
    • Place of Presentation
      Busan
    • Year and Date
      2009-08-24
    • Related Report
      2009 Final Research Report
  • [Presentation] Parkinsonism induced by tauopathy : analysis of SJLB mice.2009

    • Author(s)
      Taizo Taniguchi, Kei-ichi Kadoyama, Mariko Takenokuchi, Susumu Chiba, Noboru Suzuki, Akira Matsumoto
    • Organizer
      The 2009 ISN/APSN joint meeting
    • Place of Presentation
      Busan, Korea
    • Year and Date
      2009-08-24
    • Related Report
      2009 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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