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Novel Preventive Strategy for Alzheimer's Disease Based on the Toxic Conformation Theory of Amyloid beta

Research Project

Project/Area Number 26221202
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Bioorganic chemistry
Research InstitutionKyoto University

Principal Investigator

Irie Kazuhiro  京都大学, 農学研究科, 教授 (00168535)

Co-Investigator(Kenkyū-buntansha) 久米 利明  富山大学, 大学院医学薬学研究部(薬学), 教授 (10303843)
清水 孝彦  千葉大学, 大学院医学研究院, 講師 (40301791)
徳田 隆彦  京都府立医科大学, 医学(系)研究科(研究院), 教授 (80242692)
村上 一馬  京都大学, 農学研究科, 准教授 (80571281)
喜田 昭子  京都大学, 複合原子力科学研究所, 助教 (70273430)
Project Period (FY) 2014-05-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥164,450,000 (Direct Cost: ¥126,500,000、Indirect Cost: ¥37,950,000)
Fiscal Year 2018: ¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000)
Fiscal Year 2017: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
Fiscal Year 2016: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
Fiscal Year 2015: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2014: ¥66,170,000 (Direct Cost: ¥50,900,000、Indirect Cost: ¥15,270,000)
Keywordsアルツハイマー病 / アミロイドβ / 毒性ターン / 凝集 / 抗体 / 脳脊髄液 / 診断 / フラボノイド / 脳神経疾患 / 有機化学 / 核酸アプタマー / ノックインマウス / 毒性オリゴマー / アルツハイマー / オリゴマー / 神経細胞毒性
Outline of Final Research Achievements

Aggregation (oligomerization) of amyloid β42 (Aβ42) is considered to cause the pathogenesis of Alzheimer's disease. We identified the toxic turn at positions 22 and 23 of Aβ42 which could play an important role in the pathogenesis of AD, and developed a new anti-toxic turn antibody 24B3. Using 24B3, we proposed a new diagnostic method against AD by measuring the amount of the toxic conformer in cerebrospinal fluid. Moreover, administration of 24B3 to AD model mice mitigated their cognitive impairment.
Based on the significance of the toxic turn, we synthesized the toxic dimer and trimer models with a linker at the C-terminal region of Aβ, and showed that these models existed as quasi-stable oligomers with significant neurotoxicity. Cumulative investigations suggested the usefulness of flavonoids in AD prevention, thereby offering three structural features involved in the suppression of Aβ42 aggregation.

Academic Significance and Societal Importance of the Research Achievements

本研究代表者らが提唱した「毒性配座理論」に基づき,Aβ42の準安定な2及び3量体モデルを初めて合成した点において学術的意義があると考えている.また社会的意義としては,抗原構造が明確な抗毒性オリゴマー抗体・24B3を用いて,ヒト脳脊髄液による新しいAD診断法を提案したことが挙げられる.今後,デジタルELISA法(SimoaTM装置)と今回新たに作成した抗毒性2量体特異抗体・48D4を用いて検出感度を上げることにより,ADの早期血液診断につながる可能性がある.さらに,24B3ならびに48D4抗体はAβ42による神経細胞毒性を低濃度で抑制したことから,ヒト化することにより治療薬への応用も期待できる.

Assessment Rating
Verification Result (Rating)

A

Assessment Rating
Result (Rating)

A: Progress in the research is steadily towards the initial goal. Expected research results are expected.

Report

(11 results)
  • 2019 Research Progress Assessment (Verification Result) ( PDF )
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Abstract ( PDF )   Annual Research Report
  • Products Report
  • Research Products

    (81 results)

All 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (29 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 24 results,  Open Access: 11 results,  Acknowledgement Compliant: 8 results) Presentation (44 results) (of which Int'l Joint Research: 6 results,  Invited: 14 results) Book (1 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] The Johns Hopkins University(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Detection of Dietary Chalcone and Flavonoid Metabolites in Mice Using UPLC-MS/MS and Their Modulatory Effects on Amyloid β Aggregation2023

    • Author(s)
      Taniwa Kota, Murakami Kazuma, Sakaguchi Yoshiki, Izuo Naotaka, Hanaki Mizuho, Sampa Nobuaki, Kume Toshiaki, Shimizu Takahiko, Irie Kazuhiro
    • Journal Title

      Journal of Agricultural and Food Chemistry

      Volume: 71 Issue: 39 Pages: 14289-14299

    • DOI

      10.1021/acs.jafc.3c02598

    • Related Report
      Products Report
    • Peer Reviewed
  • [Journal Article] APP Knock-In Mice Produce E22P-Aβ Exhibiting an Alzheimer’s Disease-like Phenotype with Dysregulation of Hypoxia-Inducible Factor Expression2022

    • Author(s)
      Maki Takahito、Sawahata Masahito、Akutsu Ichiro、Amaike Shohei、Hiramatsu Genki、Uta Daisuke、Izuo Naotaka、Shimizu Takahiko、Irie Kazuhiro、Kume Toshiaki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 21 Pages: 13259-13259

    • DOI

      10.3390/ijms232113259

    • Related Report
      Products Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysine-targeting inhibition of amyloid β oligomerization by a green perilla-derived metastable chalcone in vitro and in vivo.2022

    • Author(s)
      Murakami, K., Sakaguchi, Y., Taniwa, K., Izuo, N., Hanaki, M., Kawase, T., Hirose, K., Nagao, C., Mizoguchi, K., Shimizu, T., Irie, K.
    • Journal Title

      RSC Chem. Biol.

      Volume: 3 Issue: 12 Pages: 1380-1396

    • DOI

      10.1039/d2cb00194b

    • Related Report
      Products Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a Novel Alzheimer's Disease Model Based on the Theory of the Toxic-conformer of Amyloid β2021

    • Author(s)
      泉尾直孝、清水孝彦、村上一馬、入江一浩
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 141 Issue: 6 Pages: 843-849

    • DOI

      10.1248/yakushi.20-00251-5

    • NAID

      130008046322

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2021-06-01
    • Related Report
      Products Report
    • Peer Reviewed / Open Access
  • [Journal Article] Searching for natural products that delay nucleation phase and promote elongation phase of amyloid beta42 toward Alzheimer's disease therapeutics2021

    • Author(s)
      Murakami Kazuma, Horii Shiori, Hanaki Mizuho, Irie Kazuhiro
    • Journal Title

      ACS Chemical Neuroscience

      Volume: 12 Issue: 18 Pages: 3467-3476

    • DOI

      10.1021/acschemneuro.1c00489

    • Related Report
      Products Report
    • Peer Reviewed
  • [Journal Article] アミロイドタンパク質を認識する核酸アプタマー2021

    • Author(s)
      村上一馬、入江一浩
    • Journal Title

      化学と生物

      Volume: 59 Pages: 216-218

    • Related Report
      Products Report
  • [Journal Article] Detection of amyloid β oligomers with RNA aptamers in AppNL-G-F/NL-G-F Mice: a model of Arctic Alzheimer’s disease2020

    • Author(s)
      Obata Yayoi、*Murakami Kazuma、Kawase Taiji、Hirose Kenji、Izuo Naotaka、Shimizu Takahiko、*Irie Kazuhiro
    • Journal Title

      ACS Omega

      Volume: 5 Issue: 34 Pages: 21531-21537

    • DOI

      10.1021/acsomega.0c02134

    • Related Report
      Products Report
    • Peer Reviewed / Open Access
  • [Journal Article] An RNA aptamer with potent affinity for a toxic dimer of amyloid β42 has potential utility for histochemical studies of Alzheimer's disease2020

    • Author(s)
      Murakami Kazuma, Obata Yayoi, Sekikawa Asa, Ueda Haruka, Awano Tatsuya, Takabe Keiji, Takahiko Shimizu, Irie Kazuhiro
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 295 Issue: 15 Pages: 4870-4880

    • DOI

      10.1074/jbc.ra119.010955

    • Description
      in press
    • Related Report
      Products Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthetic and biochemical studies on the effect of persulfidation on disulfide dimer models of amyloid β42 at position 35 in Alzheimer's etiology2020

    • Author(s)
      Murakami Kazuma, Kato Haruka, Hanaki Mizuho, Monobe Yoko, Akagi Ken-ichi, Kawase Taiji, Hirose Kenji, Irie Kazuhiro
    • Journal Title

      RSC Advances

      Volume: 10 Issue: 33 Pages: 19506-19512

    • DOI

      10.1039/d0ra03429k

    • Related Report
      Products Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis and Structure-Function Analyses of the Toxic Dimer and Trimer Models of Amyloid β2019

    • Author(s)
      Irie Kazuhiro
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan

      Volume: 77 Issue: 12 Pages: 1201-1208

    • DOI

      10.5059/yukigoseikyokaishi.77.1201

    • NAID

      130007760861

    • ISSN
      0037-9980, 1883-6526
    • Year and Date
      2019-12-01
    • Related Report
      Products Report
    • Peer Reviewed
  • [Journal Article] Synthesis and biochemical characterization of quasi-stable trimer models of full-length amyloid β40 with a toxic conformation2019

    • Author(s)
      Irie Yumi、Hanaki Mizuho、Murakami Kazuma、Imamoto Tsuneo、Furuta Takumi、Kawabata Takeo、Kawase Taiji、Hirose Kenji、Monobe Yoko、Akagi Ken-ichi、Yanagita Ryo C.、Irie Kazuhiro
    • Journal Title

      Chemical Communications

      Volume: 55 Issue: 2 Pages: 182-185

    • DOI

      10.1039/c8cc08618d

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An App knock-in mouse inducing the formation of a toxic conformer of Aβ as a model for evaluating only oligomer-induced cognitive decline in Alzheimer's disease2019

    • Author(s)
      Izuo Naotaka, Murakami Kazuma, Fujihara Yoshitaka, Maeda Masahiro, Saito Takashi, Saido C. Takaomi, Irie Kazuhiro, Shimizu Takahiko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 515 Issue: 3 Pages: 462-467

    • DOI

      10.1016/j.bbrc.2019.05.131

    • Related Report
      Products Report
    • Peer Reviewed
  • [Journal Article] New diagnostic method for Alzheimer's disease based on the toxic conformation theory of amyloid β2019

    • Author(s)
      Irie Kazuhiro
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 84 Issue: 1 Pages: 1-16

    • DOI

      10.1080/09168451.2019.1667222

    • NAID

      120006800709

    • Related Report
      Products Report
    • Peer Reviewed
  • [Journal Article] Three structural features of functional food components and herbal medicine with amyloid β42 anti-aggregation properties2019

    • Author(s)
      Murakami Kazuma, Irie Kazuhiro
    • Journal Title

      Molecules

      Volume: 24 Issue: 11 Pages: 2125-2125

    • DOI

      10.3390/molecules24112125

    • NAID

      120006644072

    • Related Report
      Products Report
    • Peer Reviewed / Open Access
  • [Journal Article] Change of Amyloid-β 1-42 Toxic Conformer Ratio After Cerebrospinal Fluid Diversion Predicts Long-Term Cognitive Outcome in Patients with Idiopathic Normal Pressure Hydrocephalus2018

    • Author(s)
      Akiba C, Nakajima M, Miyajima M, Ogino I, Motoi Y, Kawamura K, Adachi S, Kondo A, Sugano H, Tokuda T, Irie K, Arai H
    • Journal Title

      J Alzheimers Dis.

      Volume: 25 Issue: 3 Pages: 989-1002

    • DOI

      10.3233/jad-180059

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amyloid β toxic conformer has dynamic localization in the human inferior parietal cortex in absence of amyloid plaques2018

    • Author(s)
      Kageyama Yusuke、Saito Atsushi、Pletnikova Olga、Rudow Gay L.、Irie Yumi、An Yang、Murakami Kazuma、Irie Kazuhiro、Resnick Susan M.、Fowler David R.、Martin Lee J.、Troncoso Juan C.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 16895-16895

    • DOI

      10.1038/s41598-018-35004-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of the carboxy groups of triterpenoids in their inhibition of the nucleation of amyloid β42 required for forming toxic oligomers2018

    • Author(s)
      Murakami Kazuma、Yoshioka Takuya、Horii Shiori、Hanaki Mizuho、Midorikawa Satohiro、Taniwaki Shinji、Gunji Hiroki、Akagi Ken-ichi、Kawase Taiji、Hirose Kenji、Irie Kazuhiro
    • Journal Title

      Chemical Communications

      Volume: 54 Issue: 49 Pages: 6272-6275

    • DOI

      10.1039/c8cc03230k

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アミロイドβ「毒性コンホマー」を標的にしたアルツハイマー病の治療・診断法の開発2018

    • Author(s)
      泉尾直孝、清水孝彦、村上一馬、入江一浩
    • Journal Title

      医薬品医療機器レギュラトリーサイエンス

      Volume: 49 Pages: 312-318

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Mechanistic analyses of the suppression of amyloid β42 aggregation by apomorphine2018

    • Author(s)
      Mizuho Hanaki, Kazuma Murakami, Sumie Katayama, Ken-ichi Akagi, Kazuhiro Irie
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 26 Issue: 8 Pages: 1538-1546

    • DOI

      10.1016/j.bmc.2018.01.028

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A toxic conformer of Aβ42 with a turn at 22-23 is a novel therapeutic target for Alzheimer’s disease2017

    • Author(s)
      Naotaka Izuo, Chihiro Kasahara, Kazuma Murakami, Toshiaki Kume, Masahiro Maeda, Kazuhiro Irie, Koutaro Yokote, Takahiko Shimizu
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 11811-11811

    • DOI

      10.1038/s41598-017-11671-6

    • NAID

      120006368174

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 食品・生薬成分によるアミロイドβ42の凝集抑制機構の系統的解析2017

    • Author(s)
      村上一馬、入江一浩
    • Journal Title

      日本認知症学会誌

      Volume: 31 Pages: 351-360

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Synthetic models of quasi-stable amyloid β40 oligomers with significant neurotoxicity2017

    • Author(s)
      Yumi Irie, Kazuma Murakami, Mizuho Hanaki, Yusuke Hanaki, Takashi Suzuki, Yoko Monobe, Tomoyo Takai, Ken-ichi Akagi, Taiji Kawase, Kenji Hirose, Kazuhiro Irie
    • Journal Title

      ACS Chem. Neurosci.

      Volume: 8 Issue: 4 Pages: 807-816

    • DOI

      10.1021/acschemneuro.6b00390

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Monoclonal antibody with conformational specificity for a toxic conformer of amyloid β42 and its application toward the Alzheimer's disease diagnosis2016

    • Author(s)
      Kazuma Murakami, Maki Tokuda, Takashi Suzuki, Yumi Irie, Mizuho Hanaki, Naotaka Izuo, Yoko Monobe, Ken-ichi Akagi, Ryotaro Ishii, Harutsugu Tatebe, Takahiko Tokuda, Masahiro Maeda, Toshiaki Kume, Takahiko Shimizu, Kazuhiro Irie
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 29038-29038

    • DOI

      10.1038/srep29038

    • NAID

      120005774689

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Semisynthesis and structure-activity studies of Uncarinic acid C Isolated from Uncaria rhynchophylla as a specific inhibitor of the nucleation phase in amyloid β42 aggregation2016

    • Author(s)
      Takuya Yoshioka, Kazuma Murakami, Kyohei Ido, Mizuho Hanaki, Kanoko Yamaguchi, Satohiro Midorikawa, Shinji Taniwaki, Hiroki Gunji, Kazuhiro Irie
    • Journal Title

      J. Nat. Prod.

      Volume: 79 Issue: 10 Pages: 2521-2529

    • DOI

      10.1021/acs.jnatprod.6b00392

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] アルツハイマー病の正確な早期診断の実現に向けて2016

    • Author(s)
      入江一浩
    • Journal Title

      化学

      Volume: 71 (11) Pages: 41-44

    • Related Report
      2016 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Structural insights into mechanisms for inhibiting amyloid β42 aggregation by non-catechol-type flavonoids2016

    • Author(s)
      Mizuho Hanaki, Kazuma Murakami, Ken-ichi Akagi, Kazuhiro Irie*
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 24 Issue: 2 Pages: 304-313

    • DOI

      10.1016/j.bmc.2015.12.021

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis and characterization of the amyloid β40 dimer model with a linker at position 30 adjacent to the intermolecular β-sheet region2015

    • Author(s)
      Kazuma Murakami, Takashi Suzuki, Mizuho Hanaki, Yoko Monobe, Ken-ichi Akagi, Kazuhiro Irie*
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 466 Issue: 3 Pages: 463-467

    • DOI

      10.1016/j.bbrc.2015.09.051

    • NAID

      120005679859

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] アルツハイマー病様神経毒性におけるアミロイドβコンホマーの役割2015

    • Author(s)
      泉尾直孝*、村上一馬、久米利明、前田雅弘、入江一浩、清水孝彦
    • Journal Title

      基礎老化研究

      Volume: 39 Pages: 29-34

    • Related Report
      2015 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Conformation-specific antibodies to target amyloid beta oligomers and their application to immunotherapy for Alzheimer's disease2014

    • Author(s)
      Kazuma Murakami
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 78 Issue: 8 Pages: 1293-1305

    • DOI

      10.1080/09168451.2014.940275

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] アミロイドβ42の毒性オリゴマーに対する核酸アプタマーの開発研究と脳組織染色への応用2019

    • Author(s)
      村上一馬、小畑弥生、関川あさ、上田 遥、泉尾直孝、粟野達也、高部圭司、清水孝彦、入江一浩
    • Organizer
      2019年度日本農芸化学会大会(東京農大、東京)優秀発表
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分子内ジスルフィド結合形成によるアミロイドβ42の毒性配座モデルの合成と機能解析2019

    • Author(s)
      松島由佳、村上一馬、花木瑞穂、粟野達也、高部圭司、柳田 亮、入江一浩
    • Organizer
      2019年度日本農芸化学会大会(東京農大、東京)
    • Related Report
      2018 Annual Research Report
  • [Presentation] アミロイドβの凝集を抑制する食品・生薬成分の作用機構2019

    • Author(s)
      入江一浩、村上一馬
    • Organizer
      2019年度日本農芸化学会大会(東京農大、東京)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] アミロイドβの毒性配座理論を基盤としたアルツハイマー病の予防戦略2019

    • Author(s)
      入江一浩
    • Organizer
      2019年度日本農芸化学会大会(東京農大、東京)日本農芸化学会賞受賞講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] アミロイドβ42の2量体モデル由来の毒性オリゴマーに対するRNAアプタマー2018

    • Author(s)
      小畑弥生、村上一馬、関川あさ、粟野達也、髙部圭司、入江一浩
    • Organizer
      日本核酸医薬学会第4回年会(九州大学医学部百年講堂、福岡市)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分子内ジスルフィド結合形成によるアミロイドβの毒性コンホメーションの制御2018

    • Author(s)
      松島由佳、村上一馬、花木瑞穂、粟野達也、高部圭司、柳田 亮、入江一浩
    • Organizer
      第37回日本認知症学会学術集会(ロイトン札幌・札幌市教育文化会館、札幌市)
    • Related Report
      2018 Annual Research Report
  • [Presentation] RNA aptamers targeting the toxic oligomers of Aβ42 and their application to immunohistochemistry2018

    • Author(s)
      Murakami Kazuma、Obata Yayoi、Sekikawa Asa、Ueda Haruka、Izuo Naotaka、Awano Tatsuya、Takabe Keiji、Shimizu Takahiko、Irie Kazuhiro
    • Organizer
      The 45th International Symposium on Nucleic Acids Chemistry (Kyoto University Clock Tower Centennial Hall, Kyoto, Japan)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アポモルフィンによるアミロイドβ42凝集抑制機構の解析2018

    • Author(s)
      花木瑞穂、村上一馬、片山寿美枝、赤木謙一、入江一浩
    • Organizer
      2018年度日本農芸化学会大会(名城大学、名古屋市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] アミロイドβ42の毒性2量体モデルから形成されるプロトフィブリルを標的としたRNAアプタマーの開発2018

    • Author(s)
      小畑弥生、村上一馬、関川あさ、入江一浩
    • Organizer
      2018年度日本農芸化学会大会(名城大学、名古屋市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 青ジソに含まれるアミロイドβ42の凝集阻害物質の作用機構とマウスにおける生体内代謝2018

    • Author(s)
      坂口嘉紀、村上一馬、花木瑞穂、泉尾直孝、小澤祐介、粟野達也、高部圭司、川瀬泰司、廣瀬賢治、三羽伸明、久米利明、清水孝彦、入江一浩
    • Organizer
      2018年度日本農芸化学会大会(大会トピックス賞)(名城大学、名古屋市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] アミロイドβの毒性オリゴマーの構造解析に基づくアルツハイマー病の早期診断法の開発2018

    • Author(s)
      入江一浩
    • Organizer
      2018年度日本農芸化学会大会(名城大学、名古屋市)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] アミロイドβ「毒性コンホマー」を標的にしたアルツハイマー病の治療・診断法の開発2017

    • Author(s)
      泉尾直孝、久米利明、村上一馬、徳田隆彦、前田雅弘、入江一浩、清水孝彦
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] アミロイドβ40の毒性オリゴマーモデル2017

    • Author(s)
      入江由美、村上一馬、花木瑞穂、花木祐輔、鈴木天志、物部容子、高井朋代、赤木謙一、川瀬泰司、廣瀬賢治、入江一浩
    • Organizer
      2017年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Year and Date
      2017-03-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 漢方由来ウンカリン酸 C によるアミロイド β42 核形成阻害メカニズム2017

    • Author(s)
      吉岡卓也、村上一馬、花木瑞穂、緑川諭弘、谷脇慎治、郡司祐樹、川瀬泰司、廣瀬賢治、入江一浩
    • Organizer
      2017年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Year and Date
      2017-03-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] イオンモビリティー質量分析計を用いたアミロイドβオリゴマーの測定2017

    • Author(s)
      入江一浩
    • Organizer
      第65回質量分析総合討論会(つくば国際会議場、つくば市)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] アミロイドβの毒性配座理論と抗体創製2017

    • Author(s)
      村上一馬、入江一浩
    • Organizer
      認知症研究を知る若手研究者の集まり2017(湯の宿木もれび、大津市)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 生薬チョウトウコウに含まれるアミロイドβオリゴマー形成阻害物質の同定と作用機構2017

    • Author(s)
      村上一馬、吉岡卓也、井戸恭平、花木瑞穂、山口加乃子、緑川諭弘、谷脇慎治、郡司祐樹、赤木謙一、川瀬泰司、廣瀬賢治、入江一浩
    • Organizer
      第59回天然有機化合物討論会(札幌市民ホール、札幌市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経細胞毒性を有する準安定なアミロイドβの2量体モデルの合成とイオンモビリティー質量分析法による構造解析2017

    • Author(s)
      入江一浩、入江由美、村上一馬、花木瑞穂、花木祐輔、川瀬泰司、廣瀬賢治、徳田隆彦、前田雅弘
    • Organizer
      第35回メディシナルケミストリーシンポジウム(豊田講堂、名古屋市)
    • Related Report
      2017 Annual Research Report
  • [Presentation] オリゴマー仮説の視点からバイオマーカーを考える:アミロイドβの毒性配座理論2017

    • Author(s)
      村上一馬、入江一浩
    • Organizer
      第36回日本認知症学会学術集会(ANAクラウンプラザホテル金沢、金沢市)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] アミロイドβの毒性2量体モデルの合成とイオンモビリティー質量分析法による構造解析2017

    • Author(s)
      入江一浩
    • Organizer
      京都大学学際融合教育研究推進センター・生理化学研究ユニット第7回公開シンポジウム(京都大学農学部総合館、京都市)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 天然ポリフェノールによるAβ42凝集阻害機構の解明とアルツハイマー病予防の可能性2016

    • Author(s)
      村上一馬、入江一浩
    • Organizer
      第35回日本認知症学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] アミロイドβ40の2量体モデルの合成と神経細胞毒性2016

    • Author(s)
      入江由美、村上一馬、鈴木天志、花木瑞穂、花木祐輔、物部容子、高井朋代、赤木謙一、入江一浩
    • Organizer
      第35回日本認知症学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] ウンカリン酸によるアミロイドβ凝集核形成の選択的阻害2016

    • Author(s)
      吉岡卓也、村上一馬、井戸恭平、花木瑞穂、山口加乃子、緑川諭弘、谷脇慎治、郡司祐樹、入江一浩
    • Organizer
      第35回日本認知症学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Identification of the “toxic conformer” of amyloid β and its pathogenic contribution of Alzheimer's disease2016

    • Author(s)
      Naotaka Izuo, Kazuma Murakami, Toshiaki Kume, Masahiro Maeda, Kazuhiro Irie, Takahiko Shimizu
    • Organizer
      2016 Spring International Conference of the Korean Society for Gerontology
    • Place of Presentation
      Convention Hall (Daegu, Korea)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Aβ42の22-23位におけるターン構造はAβ42誘発神経毒性を調節する2016

    • Author(s)
      泉尾直孝、久米利明、村上一馬、前田雅弘、入江一浩、清水孝彦
    • Organizer
      日本基礎老化学会大会
    • Place of Presentation
      伊勢原市民文化会館(神奈川県伊勢原市)
    • Year and Date
      2016-05-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] アミロイドβの毒性コンホマーにきわめて特異的な抗体の開発とアルツハイマー病診断への応用2016

    • Author(s)
      村上一馬、徳田真樹、鈴木天志、入江由美、花木瑞穂、柳田亮、物部容子、赤木謙一、石井亮太郎、建部陽嗣、徳田隆彦、前田雅弘、久米利明、泉尾直孝、清水孝彦、入江一浩
    • Organizer
      2016年度日本農芸化学会大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] チョウトウコウに含まれるウンカリン酸Cおよびその誘導体のアミロイドβ凝集阻害活性2016

    • Author(s)
      吉岡卓也、村上一馬、花木瑞穂、緑川諭弘、谷脇慎治、郡司裕樹、入江一浩
    • Organizer
      2016年度日本農芸化学会大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] アミロイドβのラジカル化:アルツハイマー病態におけるSOD1の役割2016

    • Author(s)
      村上一馬、清水孝彦、入江一浩
    • Organizer
      第11回レドックス・ライフイノベーションシンポジウム
    • Place of Presentation
      お茶の水女子大学(東京都文京区)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Passive immunization with the toxic conformer of Aβ ameliorated behavioral abnormalities in Alzheimer’s-like model without affecting senile plaque deposition2016

    • Author(s)
      泉尾直孝、村上一馬、久米利明、入江一浩、横手幸太郎、清水孝彦
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Characterization of the monoclonal antibody (24B3) highly recognizing the toxic turn of amyloid β42 and its application to diagnosis for Alzheimer’s disease2016

    • Author(s)
      Kazuma Murakami, Mizuho Hanaki, Maki Tokuda, Ken-ichi kagi, Ryotaro Ishii, Harutsugu Tatebe, Takahiko Tokuda, Masahiro Maeda, Naotaka Izuo, Takahiko Shimizu, Kazuhiro Irie
    • Organizer
      The 8th Takeda Science Foundation Symposium on PharmaSciences “Biomolecule-based Medicinal Science: Featuring Mid-Size Drugs”
    • Place of Presentation
      Takeda Pharmaceutical Company, Ltd. (Suita, Japan)
    • Year and Date
      2016-01-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Structural insight into the inhibitory mechanism of amyloid β42 aggregation by non-catechol-type flavonoids2015

    • Author(s)
      Mizuho Hanaki, Kazuma Murakami, Ken-ichi Akagi, Kazuhiro Irie
    • Organizer
      2015 International Chemical Congress of Pacific Basin Societies (PACIFICHEM 2015)
    • Place of Presentation
      Hilton Hawaiian Villege (Honolulu, USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of monoclonal antibodies against the toxic turn of amyloid β42 and their application to diagnosis for Alzheimer’s disease2015

    • Author(s)
      Kazuma Murakami, Mizuho Sato-Hanaki, L. M. Moro, G. Giaccone, F. Tagliavini, Ken-ichi Akagi, Ryotaro Ishii, Takahiko Tokuda, Masahiko Maeda, Naotaka Izuo, Takahiko Shimzu, Kazuhiro Irie
    • Organizer
      2015 International Chemical Congress of Pacific Basin Societies (PACIFICHEM 2015)
    • Place of Presentation
      Hilton Hawaiian Villege (Honolulu, USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Aβ毒性コンホマーの選択的除去は老人班蓄積を阻害せずにアルツハイマー病モデルマウスの行動異常を改善する2015

    • Author(s)
      泉尾直孝、村上一馬、前田雅弘、久米利明、横手幸太郎、入江一浩、清水孝彦
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] アミロイドβの毒性配座理論に基づいた構造特異抗体の開発と診断薬への応用2015

    • Author(s)
      村上一馬、入江一浩
    • Organizer
      第8回たんぱく質の異常凝集とその防御・修復機構に関する研究会
    • Place of Presentation
      京都大学原子炉実験所(大阪府熊取町)
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] アミロイドβの毒性コンホマーを極めて特異的に認識する抗体の開発とAD診断への応用2015

    • Author(s)
      村上一馬、花木瑞穂、赤木謙一、石井亮太郎、徳田隆彦、前田雅弘、泉尾直孝、清水孝彦、入江一浩
    • Organizer
      第34回日本認知症学会学術集会
    • Place of Presentation
      リンクステーションホール青森(青森県青森市)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Aβ 毒性コンホマーの選択的除去は老人斑に影響せずアルツハイマー病症状を改善する2015

    • Author(s)
      泉尾直孝、村上一馬、前田雅弘、久米利明、横手幸太郎、入江一浩、清水孝彦
    • Organizer
      第34回日本認知症学会学術集会
    • Place of Presentation
      リンクステーションホール青森(青森県青森市)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] SOFAST-HMQC NMR を用いた非カテコール型フラボノイドによるアミロイドβの凝集抑制機構の解析2015

    • Author(s)
      花木瑞穂、村上一馬、赤木謙一、入江一浩
    • Organizer
      2015年度日本農芸化学会中部・関西支部合同大会
    • Place of Presentation
      富山県立大学(富山県射水市)
    • Year and Date
      2015-09-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非カテコール型フラボノイドによるアミロイドβの凝集抑制機構2015

    • Author(s)
      花木瑞穂、村上一馬、赤木謙一、入江一浩
    • Organizer
      第57回天然有機化合物討論会
    • Place of Presentation
      神奈川県民ホール(神奈川県横浜市)
    • Year and Date
      2015-09-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] アミロイドβペプチドの毒性配座理論に基づいた構造特異抗体の開発と診断薬への応用2015

    • Author(s)
      村上一馬、入江一浩
    • Organizer
      第47回若手ペプチド夏の勉強会
    • Place of Presentation
      信州塩尻・天然温泉アスティかたおか(長野県塩尻市)
    • Year and Date
      2015-08-11
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] アミロイドβの「毒性コンホマー」を標的とした受動免疫療法はアルツハイマー病モデルの神経症状を改善する2015

    • Author(s)
      泉尾直孝、村上一馬、徳田隆彦、久米利明、赤池昭紀、白澤卓二、横手幸太郎、入江一浩、清水孝彦
    • Organizer
      日本基礎老化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-06-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] Inhibitory mechanism for amyloid β42 aggregation by flavonoids2015

    • Author(s)
      Kazuhiro Irie
    • Organizer
      The 2nd Kyoto-Bordeaux Symposium 2015
    • Place of Presentation
      Kyoto University (Kyoto, Japan)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アミロイドβ42ダイマーの合成と活性評価2015

    • Author(s)
      徳田真樹、村上一馬、鈴木天志、花木瑞穂、岩崎真実、久米利明、入江一浩
    • Organizer
      2015年度日本農芸化学会大会
    • Place of Presentation
      岡山大学津島キャンパス(岡山市)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pathophysiological activities of the “toxic conformer” and the “non-toxic conformer” of amyloid β-induced neurotoxicity2015

    • Author(s)
      泉尾直孝、久米利明、村上一馬、入江一浩、泉 安彦、赤池昭紀、横手幸太郎、清水孝彦
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-03-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Synthesis and biological activities of the Abeta40 dimer with toxic conformation2014

    • Author(s)
      Kazuhiro Irie, Kazuma Murakami, Takashi Suzuki, Mizuho Sato, Mami Iwasaki, Toshiaki Kume
    • Organizer
      Alzheimer’s Association International Conference 2014
    • Place of Presentation
      Bella Center A/S (Copenhagen, Denmark)
    • Year and Date
      2014-07-14
    • Related Report
      2014 Annual Research Report
  • [Book] 認知症 発症前治療のために解明すべき分子病態は何か?2017

    • Author(s)
      森 啓
    • Total Pages
      252
    • Publisher
      羊土社
    • ISBN
      9784758103640
    • Related Report
      2017 Annual Research Report
  • [Remarks] 生命有機化学

    • URL

      http://www.orgchem.kais.kyoto-u.ac.jp

    • Related Report
      2018 Annual Research Report
  • [Remarks] 生命有機化学分野

    • URL

      http://www.orgchem.kais.kyoto-u.ac.jp/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 生命有機化学研究室(京都大学農学研究科食品生物科学専攻)

    • URL

      http://www.orgchem.kais.kyoto-u.ac.jp/

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Remarks] 生命有機化学研究室 食品生物科学専攻

    • URL

      http://www.orgchem.kais.kyoto-u.ac.jp/research.php?id=1

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] アミロイドβの22位及び23位のターン構造を極めて特異的に認識する抗体(学内整理番号:4718)2015

    • Inventor(s)
      入江一浩,村上一馬,清水孝彦,泉尾直孝,清藤 勉
    • Industrial Property Rights Holder
      入江一浩,村上一馬,清水孝彦,泉尾直孝,清藤 勉
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-12-14
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] アミロイドβの22位及び23位のターン構造を極めて特異的に認識する抗体2014

    • Inventor(s)
      入江一浩,村上一馬,清水孝彦,泉尾直孝,清藤 勉
    • Industrial Property Rights Holder
      入江一浩,村上一馬,清水孝彦,泉尾直孝,清藤 勉
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-251898
    • Filing Date
      2014-12-12
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-06-05   Modified: 2024-03-28  

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