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A role of spleen in the conformational transition of prion protein

Research Project

Project/Area Number 16590857
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTokushima Bunri University (2005-2007)
Fukuoka University (2004)

Principal Investigator

MATSUNAGA Yoichi  Tokushima Bunri University, Pyarmacology, Professor (80239053)

Co-Investigator(Kenkyū-buntansha) YAMADA Tatsuo  Fukuoka University, Internal Medicine, Professor (60159217)
毛利 資郎  九州大学, 大学院・医学研究科, 教授 (40117271)
藤木 富士夫  福岡大学, 医学部, 助手 (60352259)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsprion / Amyloid-beta / neurotoxicity / dendritic cells / splenocytes / breaker peptides / stefin B / moltenglobule / プリオン / 毒性阻止ペプチド / 神経細胞毒性 / ホーミング
Research Abstract

We explored the dynamics of 3 kinds of prion short peptides that is PrP101, 141 and 171-200 in mouse and clarified the preferential accumulation of protease K resistant PrP101-130 in spleen. The homology of sequences between A-beta42, Stefin B and PrP101-130 suggested that His at 111, Val at 120, Gly at 131 are the key amino acid residues to induce pathological aggregation in brain. Both of PrP and Amyloid-beta are molten-globule and we found that pH (4.6) and metal ions(Zn^<2+>, Cu^<2+>) affect the conformational transition in both Amyloid proteins. Based on the data, we explored the prion protein(PrP) breaker peptides in the mouse derived Neuronal cell(N2a). The PrP(101-130) is toxic to N2a cell and we tested 4 kinds of eight-residues peptides, namely breaker peptides PrP(101-109), PrP(103-112), PrP(115-124), PrP(128.137) to inhibit the PrP(101-130) toxicity. A potent inhibitory activity of se breaker peptides were assessed as the amount of remaining protein after PK digestion by Cell dot Western blot. In the present study, we could not find any breaker activity in these 4 peptides We also tested the same kinds of experiments to glia cells and also found no activity to inhibit the PK resistant formation. The other region of PrP peptides should be tested to inhibit the PrP(101-130) toxicity to the neuronal cells in the future study.

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (22 results)

All 2008 2007 2006 2005 2004

All Journal Article (19 results) (of which Peer Reviewed: 5 results) Presentation (3 results)

  • [Journal Article] Specific reactivity of mild/severe Alzheimer's disease patient's sera to antibody against Aβ1-40 epitope 17-212008

    • Author(s)
      Hatip F., Matsunaga Y., Yamada T.
    • Journal Title

      Acta.Neurol.Scand. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Specific reactivity of mild/severe Alzheimer's disease patient's serato antibody against Aβ1-40 epitope 17-212008

    • Author(s)
      Hatip F., Matsunaga Y., YamadaT.
    • Journal Title

      Acta.Neurol.Scand. 117(in press)

      Pages: 404-408

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific reactivity of mild/severe Alzheimer's disease patient's sera to antibody against Aβ17-212007

    • Author(s)
      Hatip F., Matsunaga Yoichi, Yamada T.
    • Journal Title

      Acta. Neurol . Scand. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] プリオン病2007

    • Author(s)
      坪井 義夫、山田 達夫
    • Journal Title

      検査と技術 35

      Pages: 426-430

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between antisocial behavior and regional cerebral blood flow in frontotemporal dementia.2006

    • Author(s)
      Nakano S., Yamada T., et al.
    • Journal Title

      Neuro Image 32

      Pages: 301-306

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes.2006

    • Author(s)
      Satoh K., Yamada T., et al.
    • Journal Title

      Brain Res. 1108

      Pages: 19-27

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Early diagnostic value of SPECT using easy Z-score imaging system in patients with neurodegenerative disease.2006

    • Author(s)
      Wqaragai M., Yamada T., et al.
    • Journal Title

      J.Neurol.Neurosurgery.Psychiat. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Amyloid-beta causes apoptosis of neuronal cells via caspase cascade,which can be prevented by Amyloid-beta-derived short peptides2005

    • Author(s)
      Awasthi A., Matsunaga Y., Yamada T.
    • Journal Title

      Exp.Neurol. 196

      Pages: 282-289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Amyloid-beta causes apoptosis of neuronal cells via caspase cascades which can be prevented by amyloid-beta derived short peptides2005

    • Author(s)
      AwasthiA., Matsunaga Y., Yamada T.
    • Journal Title

      Exp. Neurol. 19

      Pages: 282-289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Aβ causes apoptosis of neuronal cells via caspase cascade, which can be prevented by Aβ- derived short peptides.2005

    • Author(s)
      Yoichi Matsunaga, Tatsuo Yamada, Yoichi Matsunaga, Tatsuo Yamada
    • Journal Title

      Experimental Neurology 196

      Pages: 282-289

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hydrolytic activity of Aβ and its inhibition with short peptides2005

    • Author(s)
      Yoichi Matsunaga, Tatsuo Yamada
    • Journal Title

      Curr.Med.Chem.-Central Nervous System Agents 5

      Pages: 165-170

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Conformational changes preceeding Amyloid-fibril formation of Aβ, prion protein and stefin B : parallels in pH dependence.2005

    • Author(s)
      Yoichi Matsunaga, Tatsuo Yamada
    • Journal Title

      Med.Chem.Review-On line 2

      Pages: 359-367

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hydrolytic activity of amrloid-beta and its inhibition with short peptides2005

    • Author(s)
      Yoichi Matsunaga
    • Journal Title

      Curr.Med.Chem-Central Nervous system (Review) (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Conformational changes preceeding amyloid-fibril formation of amyloid-beta, prion protein and stefin B ; Paralles in pH dependence2005

    • Author(s)
      Yoichi Matsunaga
    • Journal Title

      Med.Chem. -On line Review (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Associations among plasma lipoprotein subfractions as characterized by analytical capillary isotachophoresis, apolipoprotein E phenotype Alzheimer's disease, and Mild Cognitive Impairment2005

    • Author(s)
      Tatsuo Yamada
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Eight-residue A-beta inhibit the aggregation and enzymatic activity of A-beta422004

    • Author(s)
      Matsunaga Y., Fujii A., Awasthi A., Yokotani J., Takakura T., Yamada T.
    • Journal Title

      Regul.Peptide 120

      Pages: 227-236

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Eight-residue A-beta inhibit the aggregation and enzymatic activity of A-beta 42.2004

    • Author(s)
      Matsunaga Y., Fujii A., Awasthi A., Yokotani J., Takakura T., Yamada T.
    • Journal Title

      Regul. Peptide. 120

      Pages: 227-236

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Eight-residue A-beta peptides inhibit the aggregation and enzymatic activity of A-beta422004

    • Author(s)
      Yoichi Matsunaga
    • Journal Title

      Regul.Peptides 120

      Pages: 227-236

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The effect of cholesterol and monosialoganglioside (GM1) on the release and aggregation of Amyloid beta-peptide frome liposomes prepared from brain membrane-like lipids2004

    • Author(s)
      Tatsuo Yamada
    • Journal Title

      J.Biol.Chem 279

      Pages: 17587-17595

    • Related Report
      2004 Annual Research Report
  • [Presentation] In vivo reversal of memory impairment and cellular changes induced by aged A-beta40 by breaker peptides bilaterally injected into rat Amygdale2007

    • Author(s)
      Matsunaga Y., Bolukbasi E., Kaya CZ., Gurdal N., Hatip I.
    • Organizer
      8th international conference AD/PD
    • Place of Presentation
      Salzburg
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Tau gene nucleotide substitution upstream of exon 3 in a family of dementia2007

    • Author(s)
      Kobayasi T., Yamada T.
    • Organizer
      8th International conference AD/PD
    • Place of Presentation
      Salzburg
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] In vivo reversal of memory impairment and cellular Changes induced by aged A-beta40 by breaker peptide Bilaterally injected into rat amygdale.2007

    • Author(s)
      Matsunaga Y., Bolukbasi E., Kaya CZ., Gurdal N., Hatip I.
    • Organizer
      8th International conference AD/PD
    • Place of Presentation
      Salzburg
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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