Analyses of the oligomers of amyloid beta by NMR/MRI and protein science

• Project/Area Number: 16K15110
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: TERASAWA HIROAKI 熊本大学, 大学院生命科学研究部(薬), 教授 (10300956)
• Co-Investigator(Renkei-kenkyūsha): YOSHINAGA Sosuke 熊本大学, 大学院生命科学研究部(薬), 講師 (00448515) ; TAKEDA Mitsuhiro 熊本大学, 大学院生命科学研究部(薬), 助教 (90508558) ; SAIDO Takaomi 国立研究開発法人理化学研究所, 脳科学総合研究センター, 教授 (80205690)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 認知症 / アミロイドβ / 神経毒性オリゴマー / 構造生物学

Outline of Final Research Achievements

Amyloid beta (Abeta) is often bound　in　the　brain　of　patients　with　Alzheimer　disease　as　insoluble　aggregates.　It is generally asumed that soluble ogligomer that occur before the aggregates exerts strong neurotoxicty. In this study, we explored the interaction mode of two monomers comprisng the Abeta dimer that is the minimal component of Abeta oligoemrs, using NMR, photo-induced cross coupling and mass analyses. The results showed that the two monomers aling in both parallel and anti-parallel manner in a 2:1 ratio, indicating that both the two forms exist, but the parallel one is more preferred.

Research Products

• [Presentation] Photo cross-linking and MS analyses of the amyloid β-peptide oligomers (2017)
  • Author(s): Mai Kawashita, Shintaro Yoshida, Sosuke Yoshinaga, Mitsuhiro Takeda, Ayumi Tanaka, Takashi Hamaguchi, Hitomi Yamaguchi1, Shigeto Iwamoto, Takashi Saito, Yoshihiko Takinami, Toshiyuki Kohno, Takaomi C. Saido, Hiroaki Terasawa
  • Organizer: 第５５回生物物理学会
• [Presentation] 光架橋法と質量分析法を用いたアミロイドベータペプチド（Aβ）のオリゴマー形成メカニズムの解析 (2017)
  • Author(s): 川下真依, 吉田晋太郎, 吉永壮佐, 武田光広, 田中愛弓, 濱口貴史, 山口瞳, 岩本成人, 斉藤貴志, 瀧浪欣彦, 瀬田丈士, 河野俊之, 西道隆臣, 寺沢宏明
  • Organizer: 第３６回日本認知症学会
• [Presentation] ESI-QTOF MS analyses of the oligomerization mechanism of amyloid β peptides (2016)
  • Author(s): Yoshida, S., Yoshinaga, S., Takeda, M., Tanaka, A., Hamaguchi, T., Yamaguchi, H., Iwamoto, H., Saito, T., Takinami, Y., Kohno, T., Saido, T.C., and Terasawa, H.
  • Organizer: 日本生物物理学会第５４回年会
  • Place of Presentation: つくば国際会議場、茨城
  • Year and Date: 2016-11-25