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Elucidation of molecular basis for the pathogenesis of AA amyloidosis based on the compositional analysis of biomolecules

Research Project

Project/Area Number 15K08436
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKobe Pharmaceutical University

Principal Investigator

Tanaka Masafumi  神戸薬科大学, 薬学部, 講師 (40411904)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsアミロイドーシス / 血清アミロイドA / 高密度リポタンパク質 / グリコサミノグリカン / ペプチドライゲーション
Outline of Final Research Achievements

Human serum amyloid A (SAA) is a precursor protein of AA amyloidosis. Besides an increase in blood levels of SAA, interactions between SAA and other biological components contribute to the onset of AA amyloidosis. However, the molecular basis that directly links these interactions with the onset of disease has not been fully elucidated. In the present study, we aimed to clarify the influence of glycosaminoglycans and lipid constituents in high-density lipoproteins (HDLs) on the pathogenesis of AA amyloidosis. Our research revealed that the highly sulfated domains in heparan sulfate and the concentration of phosphatidic acid in HDLs affect the onset of AA amyloidosis. In the future, we will continue to evaluate the underlying mechanism of AA amyloidosis at the molecular level by evaluating the cytotoxicity of aggregates formed by SAA.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016 2015

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Acceleration of Amyloid Fibril Formation by Carboxyl-Terminal Truncation of Human Serum Amyloid A2018

    • Author(s)
      Tanaka M., Kawakami T., Okino N., Sasaki K., Nakanishi K., Takase H., Yamada T., Mukai T.
    • Journal Title

      Arch. Biochem. Biophys.

      Volume: 639 Pages: 9-15

    • DOI

      10.1016/j.abb.2017.12.016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Lipid Environment on Amyloid Fibril Formation of Human Serum Amyloid A2017

    • Author(s)
      Tanaka M., Nishimura A., Takeshita H., Takase H., Yamada T., Mukai T.
    • Journal Title

      Chem. Phys. Lipids

      Volume: 202 Pages: 6-12

    • DOI

      10.1016/j.chemphyslip.2016.11.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structural Requirements of Glycosaminoglycans for Facilitating Amyloid Fibril Formation of Human Serum Amyloid A2016

    • Author(s)
      Takase H., Tanaka M., Yamamoto A., Watanabe S., Takahashi S., Nadanaka S., Kitagawa H., Yamada T., Mukai T.
    • Journal Title

      Amyloid

      Volume: 印刷中 Issue: 2 Pages: 67-75

    • DOI

      10.3109/13506129.2016.1168292

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Effect of Carboxyl-Terminal Truncation on Amyloid Fibril Formation of Human Serum Amyloid A2018

    • Author(s)
      Masafumi Tanaka, Toru Kawakami, Toshiyuki Yamada, Takahiro Mukai
    • Organizer
      16th International Symposium on Amyloidosis
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] AAアミロイドーシスで沈着するSAA(1-76)ペプチドの線維形成能評価2016

    • Author(s)
      田中将史、沖野希、高瀬ひろか、川上徹、山田俊幸、向高弘
    • Organizer
      第4回日本アミロイドーシス研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-08-19
    • Related Report
      2016 Research-status Report
  • [Presentation] AAアミロイドーシス発症に及ぼすグリコサミノグリカン硫酸基の影響2016

    • Author(s)
      田中将史、高瀬ひろか、関山慶紀、灘中里美、北川裕之、向高弘
    • Organizer
      第63回日本生化学会近畿支部例会
    • Place of Presentation
      神戸
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 血清アミロイドA(1-76)ペプチドの合成とアミロイド線維形成能評価2016

    • Author(s)
      沖野希、田中将史、高瀬ひろか、川上徹、山田俊幸、向高弘
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] SAAの構造特性2015

    • Author(s)
      田中将史
    • Organizer
      AASAA(AAアミロイドーシスと血清アミロイドA)研究会
    • Place of Presentation
      東京
    • Year and Date
      2015-08-22
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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