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2008 Fiscal Year Final Research Report

Molecular pathogenesis of dialysis-related amyloidosis-A fusion of the in vitro model and the animal model-

Research Project

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Project/Area Number 18390120
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionUniversity of Fukui

Principal Investigator

NAIKI Hironobu  University of Fukui, 医学部, 教授 (10227704)

Co-Investigator(Kenkyū-buntansha) HASEGAWA Kazuhiro  福井大学, 医学部, 助教 (60324159)
OOKOSHI Tadakazu  福井大学, 医学部, 助教 (90362037)
HIGUCH Keiichi  信州大学, 大学院・医学研究科, 教授 (20173156)
GOTO Yuji  大阪大学, 蛋白質研究所, 教授 (40153770)
Project Period (FY) 2006 – 2008
Keywords透析アミロイドーシス / β2-ミクログロブリン / アミロイド線維 / 試験管内分子間相互作用 / トランスジェニックマウス
Research Abstract

本研究でわれわれは、長期血液透析患者に発症するβ2-ミクログロブリン(β2-m)アミロイドーシス発症の分子機構解明を目指し、リゾフォスファチジン酸など一部のリゾリン脂質、各種遊離脂肪酸等、陰性荷電を有する生体界面活性分子が、生理的条件下におるβ2-mアミロイド線維の試験管内伸長反応を促進することを明らかにした。また、モデル動物の確立を目指し、ヒトβ2-mトランスジェニックマウスを作成した。

  • Research Products

    (19 results)

All 2009 2008 2007 2006

All Journal Article (14 results) Presentation (4 results) Book (1 results)

  • [Journal Article] A comprehensive model for packing and hydration for amyloid fibrils of β2-microglobulin2009

    • Author(s)
      Lee, Y-H., Chatani, E., Sasahara, K., Naiki, H., Goto, Y.
    • Journal Title

      J. Biol. Chem 284(4)

      Pages: 2169-2175

  • [Journal Article] Destruction of amyloid fibrils of a β2-microgobulin fragment by laser beam irradiation2009

    • Author(s)
      Ozawa, D., Yagi, H., Ban, T.Kameda, A., Kawakami,T., Naiki, H., Goto, Y.
    • Journal Title

      J. Biol. Chem 284(2)

      Pages: 1009-1017

  • [Journal Article] Growth of β2-microglobulin-related amyloid fibrils by non-esterified fatty acids at a neutral pH2008

    • Author(s)
      Hasegawa, K., Tsutsumi-Yasuhara, S., Ookoshi, T., Ohhashi,Y., Kimura, H., Takahashi, N., Yoshida, H., Miyazaki, R., Goto, Y., Naiki, H.
    • Journal Title

      Biochem.J 416(2)

      Pages: 307-315

  • [Journal Article] Lysophospholipids induce the nucleation and extension of β2-microglobulin-related amyloid fibrils at a neutral pH2008

    • Author(s)
      Ookoshi, T. Hasegawa, K., Ohhashi, Y., Kimura, H., Takahashi, N., Yoshida, H., Miyazaki, R., Goto, Y., Naiki, H.
    • Journal Title

      Nephrol. Dial. Transplant 23(10)

      Pages: 3247-3255

  • [Journal Article] Procollagen C-proteinase enhancer-1(PCPE-1)interacts with β2-microglobulin(β2-m)and may help initiate β2-m amyloid fibril formation in connective tissues2008

    • Author(s)
      Morimoto, H., Wada, J., Font, B., Mott, J.D., Hulmes D.J., Ookoshi, T., Naiki, H., Yasuhara, A., Nakatsuka, A., Fukuoka, K., Takatori, Y., Ichikawa, H., Akagi, S., Nakao, K., Makino, H.
    • Journal Title

      Matrix Biol 27(3)

      Pages: 211-219

  • [Journal Article] Visualization and classification of amyloid β supramolecular assemblies2007

    • Author(s)
      Yagi, H., Ban, T. Morigaki, K., Naiki, H., Goto, Y.
    • Journal Title

      Biochemistry 46(51)

      Pages: 15009-15017

  • [Journal Article] Cross-seeding and cross-competition in mouse apolipoprotein A-II amyloid fibrils and protein A amyloid fibrils2007

    • Author(s)
      Yan, J., Fu, X., Ge, F., Zhang, B., Yao, J., Zhang, H., Qian, J., Tomozawa, H., Naiki, H., Sawashita, J., Mori, M., Higuchi, K.
    • Journal Title

      Am.J.Pathol 171(1)

      Pages: 172-180

  • [Journal Article] A toxic monomeric conformer of the polyglutamine protein.2007

    • Author(s)
      Nagai, Y., Inui, T., Popiel, H.A., Fujikake, N., Hasegawa, K., Urade, Y., Goto, Y., Naiki, H., Toda, T.
    • Journal Title

      Nat. Struct. Mol. Biol 14(4)

      Pages: 332-340

  • [Journal Article] The anti-amyloidogenic effect is exerted against Alzheimer's β-amyloid fibrils in vitro by preferential and reversible binding of flavonoids to the amyloid fibril structure2007

    • Author(s)
      Hirohata, M., Hasegawa, K., Tsutsumi-Yasuhara, S., Ohhashi, Y., Ookoshi, T., Ono, K., Yamada, M., Naiki, H.
    • Journal Title

      Biochemistry 46(7)

      Pages: 1888-1899

  • [Journal Article] Inhibitors of amyloid β-protein aggregation mediated by GM1-containing raft-like membranes2007

    • Author(s)
      Matsuzaki, K., Noguch, T., Wakabayashi, M., Ikeda, K., Okada, T., Ohashi, Y., Hoshino, M., Naiki, H.
    • Journal Title

      Biochim. Biophys. Acta-Biomembranes 1768(1)

      Pages: 122-130

  • [Journal Article] 3D structure of amyloid protofilaments of β2-microglobulin fragment probed by solid-state NMR2006

    • Author(s)
      Iwata, K., Fujiwara, T., Matsuki, Y., Akutsu, H., Takahashi, S., Naiki, H., Goto, Y.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. 103(48)

      Pages: 18119-18124

  • [Journal Article] Real-time and single fibril observation of the formation of amyloid β spherulitic structures2006

    • Author(s)
      Ban, T., Morigaki, K., Yagi, H., Kawasaki, T., Kobayashi, A., Yuba, S., Naiki, H., Goto, Y.
    • Journal Title

      J.Biol.Chem 281(44)

      Pages: 33677-33683

  • [Journal Article] Conformation of amyloid fibrils of β2-microglobulin probed by tryptophan mutagenesis2006

    • Author(s)
      Kihara, M., Chatani, E., Iwata, K., Yamamoto, K., Matsuura, T., Nakagawa, A., Naiki, H., Goto, Y.
    • Journal Title

      J.Biol.Chem 281(41)

      Pages: 31061-31069

  • [Journal Article] Seeding-dependent propagation and maturation of β_2-microglobulin amyloid fibrils under high pressure2006

    • Author(s)
      Chatani, E., Naiki, H., Goto, Y.
    • Journal Title

      J. Mol. Biol 359(4)

      Pages: 1086-1096

  • [Presentation] アミロイド線維形成の重合核依存性重合モデルと線維形成阻害薬の探索2009

    • Author(s)
      内木宏延, 長谷川一浩, 小野賢二郎, 山田正仁
    • Organizer
      日本薬学会第129年会シンポジウム(S-22)「アミロイドβペプチドの凝集・毒性発現の分子メカニズムの解明と低分子化合物による阻害 : アルツハイマー病の克服に向けて」
    • Place of Presentation
      京都
    • Year and Date
      20090327-28
  • [Presentation] ヒトアミロイドーシスの分子病態解明に向けて2008

    • Author(s)
      内木宏延
    • Organizer
      日本ヒトプロテオーム機構第6回大会シンポジウム「蛋白質のフォールディング病」
    • Place of Presentation
      大阪
    • Year and Date
      20080929-30
  • [Presentation] ヒトアミロイドーシスの分子病態解明に向けて : 現状と展望2008

    • Author(s)
      内木宏延
    • Organizer
      第8回日本蛋白質科学会年会シンポジウム「アミロイド構造生物学の新たな地平」
    • Place of Presentation
      東京
    • Year and Date
      20080610-12
  • [Presentation] Molecular pathogenesis of β2-microglobulin-related amyloidosis2006

    • Author(s)
      Naiki, H.
    • Organizer
      24th Annual Meeting of the International Society of Blood Purification
    • Place of Presentation
      Nara, Japan
    • Year and Date
      20060908-10
  • [Book] タンパク質の事典(編 : 猪飼篤, 伏見譲, 卜部格, 上野川修一, 中村春木, 浜窪隆雄),"アミロイドタンパク質"2008

    • Author(s)
      内木宏延(分担執筆)
    • Total Pages
      109-112
    • Publisher
      朝倉書店

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Published: 2010-06-10   Modified: 2016-04-21  

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