Evaluation of cytotoxicity and control of protein aggregation in the amyloid fibril formation

• Project/Area Number: 25440027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Tottori University
• Principal Investigator: Kawata Yasushi 鳥取大学, 工学(系)研究科(研究院), 教授 (40177697)
• Co-Investigator(Renkei-kenkyūsha): MIZOBATA TOMOHIRO 鳥取大学, 大学院工学研究科, 准教授 (50263489)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: タンパク質 / アミロイド線維 / タンパク質凝集抑制 / 神経変性病 / 凝集抑制 / 細胞毒性 / アントシアニン / SOD1 / Aβペプチド / 蛋白質凝集 / αシヌクレイン / アミノ酸電荷 / GroES / ポリフェノール

Outline of Final Research Achievements

We clarified the characteristics and mechanism of amyloid fibril formation of neurodegenerative disease causative proteins, such as alpha-synuclein, SOD1, and A-beta peptide, at amino acid level. We also evaluated cytotoxicity of the molecular species during amyloid fibril or aggregates formation process in the presence or absence of anthocyanins. We found that anthocyanins suppressed amyloid fibril formation by bypassing the protein molecules to mediate formation of amorphous aggregates that are not harmful for cells.

Research Products

• [Journal Article] Structural basis of Cu, Zn-superoxide dismutase amyloid fibril formation involves interaction of multiple peptide core regions (2016)
  • Author(s): Ida, M. Ando, M. Adachi, M. Tanaka, A. Machida, K. Hongo, K. Mizobata, T. Yamakawa, M. Y. Watanabe, Y. Nakashima, K. Kawata, Y.
  • Journal Title: Journal of Biochemistry Volume: 159 Issue: 2 Pages: 247-260
  • DOI: 10.1093/jb/mvv091
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anthocyanin suppresses the toxicity of Abeta deposits through diversion of molecular forms in in vitro and in vivo models of Alzheimer's disease (2016)
  • Author(s): Yamakawa, M. Y. Uchino, K. Watanabe, Y. Adachi, T. Nakanishi, M. Ichino, H. Hongo, K. Mizobata, T. Kobayashi, S. Nakashima, K. Kawata, Y.
  • Journal Title: Nutritional Neuroscience Volume: 19 Issue: 1 Pages: 32-42
  • DOI: 10.1179/1476830515y.0000000042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ultrasonication-dependent formation and degradation of α-synuclein amyloid fibrils (2015)
  • Author(s): Hisashi Yagi, Aiko Mizuno, Masatomo So, Miki Hirano, Masayuki Adachi, Yoko Akazawa-Ogawa, Yoshihisa Hagihara, Tatsuya Ikenoue, Young-Ho Lee, Yasushi Kawata, Yuji Goto
  • Journal Title: Biochimica et Biophysica Acta Volume: 1854 Issue: 3 Pages: 209-217
  • DOI: 10.1016/j.bbapap.2014.12.014
  • Peer Reviewed
• [Journal Article] Cold denaturation of alpha-synuclein amyloid fibrils. (2014)
  • Author(s): Ikenoue, T. , Lee, Y.-H. , Kardos, J., Sakai, M., Yagi, H., Kawata, Y. and Goto, Y.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 53 Issue: 30 Pages: 7799-7804
  • DOI: 10.1002/anie.201403815
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Bilberry anthocyanins neutralize the cytotoxicity of co-chaperonin GroES fibrillation intermediates (2013)
  • Author(s): Hisanori Iwasa, Hiroshi Kameda, Naoya Fukui, Sakiho Yoshida, Kunihiro Hongo, Tomohiro Mizobata, Saori Kobayashi, and Yasushi Kawata
  • Journal Title: Biochemistry Volume: 52 Issue: 51 Pages: 9202-9211
  • DOI: 10.1021/bi401135j
  • Peer Reviewed
• [Presentation] アントシアニンによる家族性ALS原因タンパク質SOD1 G93Aのアミロイド線維形成抑制 (2015)
  • Author(s): 安藤瑞歩，本郷邦広，溝端知宏，小林沙織，河田康志
  • Organizer: BMB2015:第３８回日本分子生物学会年会，第８８回日本生化学会大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] ALS発症原因タンパク質SOD1の構造安定性とアミロイド線維形成機構 (2015)
  • Author(s): 井田昌孝，安藤瑞歩，本郷邦広，溝端知宏，河田康志
  • Organizer: BMB2015:第３８回日本分子生物学会年会，第８８回日本生化学会大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] タンパク質の構造形成と凝集形成 (2015)
  • Author(s): 河田康志
  • Organizer: 第54回日本白内障学会総会，第４１回水晶体研究会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-09-19
  • Invited
• [Presentation] Mechanism of amyloid fibril formation of alpha-synuclein, a causative protein of Parkinson’s disease (2014)
  • Author(s): Yasushi Kawata
  • Organizer: Institute for Protein Research Seminar, JSPS Japan Hungary Joint Seminar
  • Place of Presentation: 大阪府吹田市
  • Year and Date: 2014-11-19
  • Invited
• [Presentation] αシヌクレイン蛋白質のアミロイド線維核部位に存在するPhe94とその周辺残基の線維形成おける役割解明 (2014)
  • Author(s): 齋木美裕，伊藤有未, 本郷邦広, 溝端知宏, 河田康志
  • Organizer: 第８７回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-17
• [Presentation] Structure and function of flexible protein: Chaperonin GroEL/ES and intrinsically disordered protein alpha-synuclein (2013)
  • Author(s): Yasushi Kawata
  • Organizer: The 18th Biophysics Conference
  • Place of Presentation: Taipei, Taiwan
  • Invited
• [Presentation] クリスタリン蛋白質の凝集抑制効果に関する研究 (2013)
  • Author(s): 山下智，内島諒子，本郷邦広，溝端知宏，小林沙織，河田康志
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: 鳥取，とりぎん文化会館
• [Presentation] αシヌクレインのアミロイド線維形成を抑制するキノコ由来ケミカルシャペロンの探索 (2013)
  • Author(s): 亀田 啓, 櫻井 敏彦, 本郷 邦広, 溝端 知宏, 河田 康志
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: 鳥取，とりぎん文化会館
• [Presentation] パーキンソン病原因蛋白質α-synucleinアミロイド線維のアントシアニンによる分解機構 (2013)
  • Author(s): 平川和哉，岩佐尚徳，本郷邦広，溝端知宏，小林沙織，河田康志
  • Organizer: 第13回日本蛋白質科学会年会
  • Place of Presentation: 鳥取，とりぎん文化会館
• [Presentation] タンパク質凝集形成抑制と神経変性病発症に対するアントシアニンの効果 (2013)
  • Author(s): 河田康志
  • Organizer: 第７回眼抗加齢医学研究会
  • Place of Presentation: 東京，品川グランドセントラルタワー
  • Invited
• [Remarks] 蛋白質機能学/蛋白質苦学研究室
  • URL: http://www.bio.tottori-u.ac.jp/~prot/main.html