Studies on the molecular mechanism of amyloid fibril formation and on the role of extracellular quality control mechanism in the fibril formation.

• Project/Area Number: 20570105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: University of Fukui
• Principal Investigator: HESEGAWA Kazuhiro University of Fukui, 医学部, 助教 (60324159)
• Co-Investigator(Kenkyū-buntansha): NAIKI Hironobu 福井大学, 医学部, 教授 (10227704) ; OZAWA Daisaku 福井大学, 医学部, 特命助教 (60554524)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 変性とフォールディング / アミロイド線維 / アルツハイマー病 / 透析アミロイド症 / 生物物理 / 蛋白質

Research Abstract

We constructed several amyloid fibril formation system in vitro to evaluate the roles of the various biological molecules or reaction conditions in the amyloid fibril formation. The key findings of this study are as follows : (1) Non-esterified fatty acids induce the extension of β2-microglobulin amyloid fibril at a neutral pH in vitro. (2) Air-water interface, agitation and concentrations of Aβ peptide play critical roles in the nucleation of β-amyloid fibril of Alzheimer's disease. (3) The detailed molecular mechanismof α2-macroglobulin, a human plasma protein and an extracellular molecular chaperon, in the inhibition of β2-microglobulin amyloid fibril formation was clarified.

Research Products

• [Journal Article] Inhibition of β2-microglobulin amyloid fibril formation by_a2-macroglobulin. (2011)
  • Author(s): Ozawa D, Hasegawa K, Lee YH, Sakurai K, Yanagi K, Ookoshi T, Goto Y, Naiki H.
  • Journal Title: J Biol Chem. 286(11) Pages: 9668-9676
  • Peer Reviewed
• [Journal Article] Inhibition of ss_2-microglobulin amyloid fibril formation by α_2-macroglobulin (2011)
  • Author(s): Ozawa D, et al.
  • Journal Title: J.Biol.Chem. Volume: 286 Pages: 9668-9876
  • Peer Reviewed
• [Journal Article] Critical role of interfaces and agitation on the nucleation of Abeta amyloid fibrils at low concentrations of Abeta monomers. (2010)
  • Author(s): Morinaga A, Hasegawa K, Nomura R, Ookoshi T, Ozawa D, Goto Y, Yamada M, Naiki H.
  • Journal Title: Biochim Biophys Acta. 1804(4) Pages: 986-995
  • Peer Reviewed
• [Journal Article] Critical role of interfaces and agitation on the nucleation of Ass amyloid fibrils at low concentrations of Ass monomers (2010)
  • Author(s): Morinaga A, et al.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1804 Pages: 986-995
  • Peer Reviewed
• [Journal Article] 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 (2010)
  • Author(s): 内木宏延, 他
  • Journal Title: 薬学雑誌 Volume: 130 Pages: 503-509
  • NAID: 130000259538
• [Journal Article] Critical role of interfaces and agitation on the nucleation of Aβ amyloid fibrils at low concentrations of Aβ monomers (2010)
  • Author(s): Morinaga, A., et.al.
  • Journal Title: Biochim. Biophys. Acta. 1804 Pages: 986-995
  • Peer Reviewed
• [Journal Article] Amyloid fibrils formed by selective N-, C-terminal sequences of mouse apolipoprotein A-II. (2009)
  • Author(s): Sawashita J, Kametani F, Hasegawa K, Tsutsumi-Yasuhara S, Zhang B, Yan J, Mori, M, Naiki H, Higuchi K.
  • Journal Title: Biochim Biophys Acta. 1794(10) Pages: 1517-1529
  • NAID: 120007110403
  • Peer Reviewed
• [Journal Article] Amyloid fibrils formed by selective N-, C-terminal sequences of mouse apolipoprotein A-II (2009)
  • Author(s): Sawashita, J, et al.
  • Journal Title: Biochim. Biophys. Acta. 1794 Pages: 1517-1529
  • Peer Reviewed
• [Journal Article] Growth of β2-microglobulin-related amyloid fibrils by non-esterified fatty acids at a neutral pH. (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Growth of β2-microglobulin-related amyloid fibrils by non-esterified fatty acids at a neutral pH. (2008)
  • Author(s): Hasegawa K., et al.
  • Journal Title: Biochem J. 416(2) Pages: 307-315
  • Peer Reviewed
• [Presentation] βアミロイド線維の核形成における界面の影響 (2010)
  • Author(s): 長谷川一浩、森永章義、山田正仁、内木宏延
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] α_2-Macroglobulin inhibits ss_2-microglobulin amyloid fibril formation in vitro (2010)
  • Author(s): Ozawa D, et al.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] ssアミロイド線維の核形成における界面の影響 (2010)
  • Author(s): 長谷川一浩, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Transmissible amyloid fibrils formed by selective N-, C-terminal sequences of mouse apolipoprotein A-II (2010)
  • Author(s): Sawashita J, et al.
  • Organizer: The 3rd International Symposium on Protein Community
  • Place of Presentation: Nara
  • Year and Date: 2010-09-14
• [Presentation] a_2-Macroglobulin inhibits β_2-microglobulin amyloid fibril formation in vitro. (2010)
  • Author(s): Ozawa D., Hasegawa K., Lee YH., Sakurai K., Yanagi K., Ookoshi T., Goto Y., Naiki H.
  • Organizer: The 3rd International Symposium on Protein Community
  • Place of Presentation: Nara.
  • Year and Date: 2010-09-13
• [Presentation] α_2-Macroglobulin inhibits ss_2-microglobulin amyloid fibril formation in vitro (2010)
  • Author(s): Ozawa D, et al.
  • Organizer: The 3rd International Symposium on Protein Community
  • Place of Presentation: Nara
  • Year and Date: 2010-09-13
• [Presentation] The role of interfaces and agitation on the fibril formation of amyloid β-protein. (2010)
  • Author(s): Morinaga A, Hasegawa K, Nomura R, Ookoshi T, Ozawa D, Goto Y, Yamada M, Naiki H.
  • Organizer: Alzheimer's Association International Conference on Alzheimer's Disease 2010
  • Place of Presentation: Hawaii.
• [Presentation] マウスF型apolipoprotein A-II(apoA-II)のC末アミノ酸配列はアミロイド線維形成を阻止する (2010)
  • Author(s): 澤下仁子、亀谷富由樹、長谷川 一浩、 張〓茄、王耀勇、森政之、 内木延、樋口京一
  • Organizer: 日本基礎老化学会第33回大会
  • Place of Presentation: 名古屋
• [Presentation] The role of interfaces and agitation on the fibril formation of amyloid ss-protein (2010)
  • Author(s): Morinaga A, et al.
  • Organizer: Alzheimer's Association International Conference on Alzheimer's Disease 2010
  • Place of Presentation: Hawaii
• [Presentation] 透析アミロイドーシス発症における血漿リゾリン脂質濃度の意義 (2009)
  • Author(s): 高橋直生、木村秀樹、大越忠和、長谷川 一浩、奈良雅文、宮崎良一、内木宏延、吉田治義
  • Organizer: 第52回平成21年度日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-04
• [Presentation] 遊離脂肪酸によるβ2-ミクログロブリンアミロイド線維伸長反応促進効果の解析 (2009)
  • Author(s): 大越忠和、長谷川一浩、後藤祐児、内木宏延
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
• [Presentation] 透析アミロイドーシス発症における血漿リゾリン脂質濃度の意義 (2009)
  • Author(s): 高橋直生, 他
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Remarks] ホームページ等