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Structure and molecular interactions in aggregation of amyloid beta protein

Research Project

Project/Area Number 26860020
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionUniversity of Toyama

Principal Investigator

Ikeda Keisuke  富山大学, 大学院医学薬学研究部(薬学), 助教 (00553281)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsアミロイド / 脂質膜 / 膜曲率
Outline of Final Research Achievements

Conversion of amyloid-β (Aβ) protein from a non-toxic monomer into the toxic aggregates is the possible pathogenic pathways in Alzheimer’s disease. Recent studies have suggested that lipid membranes play key roles in protein aggregation. However, the binding modes and the mechanisms of Aβ aggregation on lipid vesicles are not fully understood. Here, we observed that a high positive curvature of lipid vesicles with diameters of ~30 nm enhanced the binding of Aβ with anionic membranes in the liquid crystalline phase and with zwitterionic membranes in the gel phase. The binding modes of Aβ to these membranes differ in terms of the depth of the protein in the membrane and of the protein structure. Amyloid fibril formation of Aβ was accelerated in the presence of the vesicles. Our findings suggest that packing defects on membranes with high curvatures might result in the accumulation of toxic protein aggregates.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (10 results)

All 2016 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] High membrane curvature enhances binding, conformational changes, and fibrillation of amyloid-β on lipid bilayer surfaces2015

    • Author(s)
      Sugiura Y, Ikeda K, Nakano M.
    • Journal Title

      Langmuir

      Volume: 31 Issue: 42 Pages: 11549-11557

    • DOI

      10.1021/acs.langmuir.5b03332

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Self-Reproduction of Nanoparticles through Synergistic Self-Assembly.2015

    • Author(s)
      K. Ikeda, M. Nakano
    • Journal Title

      Langmuir

      Volume: 31 Issue: 1 Pages: 17-21

    • DOI

      10.1021/la503491p

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] pH-dependent promotion of phospholipid flip-flop by the KcsA potassium channel2015

    • Author(s)
      H. Nakao, K. Ikeda, M. Iwamoto, H. Shimizu, S. Oiki, Y. Ishihama, M. Nakano
    • Journal Title

      Biochim. Biophys. Acta-Biomembr.

      Volume: 1848 Issue: 1 Pages: 145-150

    • DOI

      10.1016/j.bbamem.2014.10.001

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Effects of Lipid Membrane Curvatures on Binding, Secondary Structure, and Aggregation of Amyloid-β Protein2016

    • Author(s)
      Yuuki Sugiura, Keisuke Ikeda, and Minoru Nakano
    • Organizer
      Biophysical society 60th annual meeting
    • Place of Presentation
      Los Angeles, California
    • Year and Date
      2016-02-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アミロイドβタンパク質の膜結合、構造変化および凝集に脂質膜曲率が与える影響2015

    • Author(s)
      杉浦裕樹、池田恵介、中野 実
    • Organizer
      膜シンポジウム2015
    • Place of Presentation
      神戸
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] Amyloid-βと脂質膜の相互作用に対する膜曲率の影響2015

    • Author(s)
      杉浦裕樹,池田恵介,中野実
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 脂質膜環境におけるアミロイドβタンパク質の構造変化と凝集2015

    • Author(s)
      池田恵介
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Amyloid-βの結合様式に対する脂質膜物性の影響2014

    • Author(s)
      杉浦裕樹,池田恵介,中野実
    • Organizer
      膜シンポジウム2014
    • Place of Presentation
      神戸
    • Year and Date
      2014-11-26 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Amyloid-βの結合様式に対する脂質膜物性の影響2014

    • Author(s)
      杉浦裕樹,池田恵介,中野実
    • Organizer
      日本薬学会北陸支部第126回例会
    • Place of Presentation
      金沢
    • Year and Date
      2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] Amyloid-βの結合様式に対する脂質膜物性の影響2014

    • Author(s)
      杉浦裕樹,池田恵介,中野実
    • Organizer
      日本膜学会第36年会
    • Place of Presentation
      東京
    • Year and Date
      2014-05-12 – 2014-05-13
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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