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Creation of drug efficacy prediction system based on ultrasensitive protein profiling using human iPS cells

Research Project

Project/Area Number 19K07119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionUniversity of Toyama

Principal Investigator

Kume Toshiaki  富山大学, 学術研究部薬学・和漢系, 教授 (10303843)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsタンパク質プロファイリング / アルツハイマー病 / 神経変性疾患 / 網羅解析 / iPS細胞
Outline of Research at the Start

難治性神経変性疾患は長期間にわたって症状が徐々に進行することから、早期からの介入によって疾患予防と進行の緩徐化が可能と考えられているが、適切なバイオマーカーが同定されておらず、実現に至っていない。本研究では、新規等電点電気泳動ゲルおよび画像解析技術を活用して、根治困難な脳疾患に対する先制医療を実現するバイオマーカーの探索とタンパク質プロファイリングによる薬物の作用点の解析系の構築を行う。

Outline of Final Research Achievements

There is currently no established fundamental treatment for neurodegenerative diseases like Alzheimer's disease (AD), and there is increasing hope for preemptive medicine through early intervention. However, no biomarkers have been discovered to facilitate its implementation. In this study, instead of solely focusing on individual protein variations, we employed protein profiling technology to comprehensively collect patterns of protein variation. Multiple protein variation patterns were then identified as potential disease biomarkers. Initially, our plan was to conduct basic research on their application. However, due to various circumstances, we shifted our focus to investigating the mechanism of toxicity manifestation in AD model mice and the three-dimensional structure of Aβ, which plays a crucial role in its onset. By doing so, we aimed to elucidate the contributing factors involved.

Academic Significance and Societal Importance of the Research Achievements

本研究により、脳疾患と関連するタンパク質のプロファイルに関する新たな知見が得られることが期待されます。これにより、脳の病理学や疾患の発症機構についてより深い理解が可能になります。また、新しいタンパク質プロファイリング技術の開発や改良は、医学研究における重要な手法の進歩を促進することが期待されます。社会的意義については、脳疾患における早期診断と個別化された治療法の開発は、患者の生活の質を向上させる重要な要素であり、バイオマーカーの創出は、脳疾患の早期検出や効果的な治療法の開発に寄与することが期待されます。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (35 results)

All 2023 2022 2021 2020 2019

All Journal Article (18 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 18 results,  Open Access: 14 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Chronic Treatment with Aβ42 with a Toxic Conformer and LPS Induces Inflammatory Responses in BV-2 Microglia with Dysregulation of Hypoxia-Inducible Factor Expression2023

    • Author(s)
      Maki Takahito、Sawahata Masahito、Uta Daisuke、Irie Kazuhiro、Kume Toshiaki
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 46 Issue: 2 Pages: 359-363

    • DOI

      10.1248/bpb.b22-00855

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2023-02-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histamine enhances ATP-induced itching and responsiveness to ATP in keratinocytes2022

    • Author(s)
      Inami Yoshihiro、Fukushima Miki、Kume Toshiaki、Uta Daisuke
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 148 Issue: 2 Pages: 255-261

    • DOI

      10.1016/j.jphs.2021.12.004

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Panaxytriol Inhibits Lipopolysaccharide-Induced Microglia Activation in Brain Inflammation <i>in Vivo</i>2021

    • Author(s)
      Hiramatsu Genki、Matsuda Kosuke、Uta Daisuke、Mihara Kenichi、Kume Toshiaki
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 44 Issue: 7 Pages: 1024-1028

    • DOI

      10.1248/bpb.b21-00288

    • NAID

      130008060341

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2021-07-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishing a high throughput drug screening system for cerebral ischemia using zebrafish larvae.2021

    • Author(s)
      Matsumoto M, Miyamoto M, Sawahata M, Izumi Y, Takada-Takatori Y, Kume T.
    • Journal Title

      J Pharmacol Sci.

      Volume: 147 Issue: 1 Pages: 138-142

    • DOI

      10.1016/j.jphs.2021.06.006

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo brain ischemia-reperfusion model induced by hypoxia-reoxygenation using zebrafish larvae.2021

    • Author(s)
      Sawahata M, Izumi Y, Akaike A, Kume T.
    • Journal Title

      Brain Res Bull.

      Volume: 173 Pages: 45-52

    • DOI

      10.1016/j.brainresbull.2021.05.003

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory effect of panaxytriol on BV-2 microglial cell activation2021

    • Author(s)
      Hiramatsu Genki、Uta Daisuke、Mihara Kenichi、Andoh Tsugunobu、Kume Toshiaki
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 145 Issue: 3 Pages: 273-278

    • DOI

      10.1016/j.jphs.2021.01.001

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective Effect of 2′,3′-Dihydroxy-4′,6′-dimethoxychalcone on Glutamate-Induced Neurotoxicity in Primary Cortical Cultures2020

    • Author(s)
      Taguchi Kazuya、Izumi Yasuhiko、Takada-Takatori Yuki、Akaike Akinori、Kume Toshiaki
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 1 Pages: 184-187

    • DOI

      10.1248/bpb.b19-00718

    • NAID

      130007779177

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-01-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fernblock Upregulates NRF2 Antioxidant Pathway and Protects Keratinocytes From PM 2.5-Induced Xenotoxic Stress.&#160;2020

    • Author(s)
      Delgado-Wicke P, Rodriguez-Luna A, Ikeyama Y, Honma Y, Kume T, Gutierrez M, Lorrio S, Juarranz , Gonzlez S.
    • Journal Title

      Oxid Med Cell Longev.

      Volume: 2020 Pages: 2908108-2908108

    • DOI

      10.1155/2020/2908108

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Protective effects of Nrf2?ARE activator on dopaminergic neuronal loss in Parkinson disease model mice: Possible involvement of heme oxygenase-12020

    • Author(s)
      Inose Yuri、Izumi Yasuhiko、Takada-Takatori Yuki、Akaike Akinori、Koyama Yutaka、Kaneko Shuji、Kume Toshiaki
    • Journal Title

      Neuroscience Letters

      Volume: 736 Pages: 135268-135268

    • DOI

      10.1016/j.neulet.2020.135268

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthetic and biophysical studies on the toxic conformer in amyloid β with the E22Δ mutation in Alzheimer pathology2020

    • Author(s)
      Murakami K, Yamaguchi T, Izuo N, Kume T, Hara H, Irie K.
    • Journal Title

      ACS Chem Neurosci.

      Volume: 11 Issue: 19 Pages: 3017-3024

    • DOI

      10.1021/acschemneuro.0c00331

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Toxic Amyloid β42 Oligomers in Rat Primary Cerebral Cortex Cells and Human iPS-derived Neurons Treated with 10-Me-Aplog-1, a New PKC Activator2020

    • Author(s)
      Murakami Kazuma、Yoshimura Mayuko、Nakagawa Shota、Kume Toshiaki、Kondo Takayuki、Inoue Haruhisa、Irie Kazuhiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 4 Pages: 1179-1179

    • DOI

      10.3390/ijms21041179

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective Effects of 2′,3′-Dihydroxy-4′,6′-dimethoxychalcone Derived from Green Perilla Leaves against UV Radiation-Induced Cell Injury in Human Cultured Keratinocytes2019

    • Author(s)
      Takada-Takatori Y, Tomii Y, Takemasa S, Takeda Y, Izumi Y, Akaike A, Tsuchida K, Kume T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 11 Pages: 1936-1941

    • DOI

      10.1248/bpb.b19-00618

    • NAID

      130007740607

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-11-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective Effect of Green Perilla-Derived Chalcone Derivative DDC on Amyloid β Protein-Induced Neurotoxicity in Primary Cortical Neurons2019

    • Author(s)
      Iwasaki M, Izuo N, Izumi Y, Takada-Takatori Y, Akaike A, Kume T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 11 Pages: 1942-1946

    • DOI

      10.1248/bpb.b19-00657

    • NAID

      130007740604

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-11-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] α-Synuclein oligomers mediate the aberrant form of spike-induced calcium release from IP3 receptor.2019

    • Author(s)
      Yamamoto K, Izumi Y, Arifuku M, Kume T, Sawada H.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 15977-15977

    • DOI

      10.1038/s41598-019-52135-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased CCL6 expression in astrocytes and neuronal protection from neuron-astrocyte interactions.2019

    • Author(s)
      Nakagawa S, Izumi Y, Takada-Takatori Y, Akaike A, Kume T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 519 Issue: 4 Pages: 777-782

    • DOI

      10.1016/j.bbrc.2019.09.030

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of 2'-3'-dihydroxy-4',6'-dimethoxychalcone derived from green perilla on auricle thickness in chronic contact dermatitis model mice.2019

    • Author(s)
      Takada-Takatori Y, Takeda Y, Imai R, Izumi Y, Akaike A, Tsuchida K, Kume T.
    • Journal Title

      J Pharmacol Sci.

      Volume: 141 Issue: 1 Pages: 17-24

    • DOI

      10.1016/j.jphs.2019.08.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Donepezil modulates amyloid precursor protein endocytosis and reduction by up-regulation of SNX33 expression in primary cortical neurons.2019

    • Author(s)
      Takada-Takatori Y, Nakagawa S, Kimata R, Nao Y, Mizukawa Y, Urushidani T, Izumi Y, Akaike A, Tsuchida K, Kume T.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 11922-11922

    • DOI

      10.1038/s41598-019-47462-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] アミロイドβの毒性コンホマーによるアルツハイマー病発症機構と低酸素誘導因子(HIF)経路の関与2023

    • Author(s)
      牧俊人, 天池将平, 澤幡雅仁, 歌大介, 泉尾直孝, 清水孝彦, 入江一浩, 久米利明
    • Organizer
      日本薬学会第143年会;
    • Related Report
      2022 Annual Research Report
  • [Presentation] Panaxytriol inhibits lipopolysaccharide-induced microglia activation in brain inflammation mouse model2021

    • Author(s)
      Hiramatsu G, Matsuda K, Uta D, Mihara K, Sawahata M, Kume T
    • Organizer
      6th Toyama-Basel Meeting 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Panaxytriol, which is an active Panax ginseng component, inhibits LPS-induced microglia activation in vitro and in vivo.2021

    • Author(s)
      Hiramatsu G, Sawahata M, Uta D, Mihara K, Kume T.
    • Organizer
      Natural Products or Healthy Aging 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Panaxytriol inhibits lipopolysaccharide induced microglia activation.2021

    • Author(s)
      Hiramatsu G, Matsuda K, Uta D, Mihara K, Kume T.
    • Organizer
      The 51th Annual Meeting of the Society for Neuroscience
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] NMDAの脳内投与がゼブラフィッシュ稚魚の脳循環及び神経細胞に与える影響.2021

    • Author(s)
      澤幡雅仁, 青山佳樹, 歌大介, 久米利明.
    • Organizer
      第7回ゼブラフィッシュ・メダカ創薬研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] 脳疾患モデル動物としてのゼブラフィッシュと難治性神経疾患研究.2021

    • Author(s)
      久米利明.
    • Organizer
      「未来へのバイオ技術」勉強会 ゼブラフィッシュ創薬
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Inhibitory effect of panaxytriol on the lipopolysaccharide-induced microglial activation.2021

    • Author(s)
      平松元気, 松田康佑, 歌大介, 三原憲一, 安東嗣修, 久米利明.
    • Organizer
      The 94th Annual Meeting of the Japan Pharmacological Society;
    • Related Report
      2020 Research-status Report
  • [Presentation] PanaxytriolはLPS誘発脳内炎症マウスモデルにおける活性化ミクログリアを抑制する.2021

    • Author(s)
      平松元気, 松田康佑, 歌大介, 三原憲一, 安東嗣修, 久米利明.
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Panaxytriolのミクログリア活性化に対する抑制作用機序の解析.2020

    • Author(s)
      平松元気, 歌大介, 三原憲一, 安東嗣修, 久米利明.
    • Organizer
      第71回日本薬理学会北部会
    • Related Report
      2020 Research-status Report
  • [Presentation] 新規アプローチを用いた脳疾患克服を目指した天然物活用研究2019

    • Author(s)
      久米利明
    • Organizer
      第65回富山県薬事研究会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 新規Nrf2-ARE活性化物質のヘムオキシゲナーゼ-1を介した抗パーキンソン病作用2019

    • Author(s)
      猪瀬由莉, 泉安彦, 片岡春恵, 小山豊, 金子周司, 久米利明
    • Organizer
      第135回日本薬理学会近畿部会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脳疾患の病態解析と治療法開発に向けた薬理学研究2019

    • Author(s)
      久米利明
    • Organizer
      富山薬総会 富山・石川合同支部記念講演
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 天然物を活用した脳疾患克服を目指した薬理学研究2019

    • Author(s)
      久米利明, 川地隆太, 泉安彦, 赤池昭紀
    • Organizer
      第35回創薬セミナー
    • Related Report
      2019 Research-status Report
  • [Presentation] Aβの立体構造に基づくアルツハイマー病治療法の開発研究2019

    • Author(s)
      久米利明
    • Organizer
      生体機能と創薬シンポジウム2019
    • Related Report
      2019 Research-status Report
  • [Presentation] ドネペジルのSorting Nexin 33発現量上昇を介したAβ抑制作用2019

    • Author(s)
      竹中未紗, 髙鳥悠記, 木全璃子, 泉安彦, 赤池昭紀, 久米利明, 土田勝晴
    • Organizer
      生体機能と創薬シンポジウム2019
    • Related Report
      2019 Research-status Report
  • [Presentation] DAT遺伝子へのインテグリンα5遺伝子ヘテロノックインES細胞の作製と神経分化効率に関する検討2019

    • Author(s)
      福澤萌香, 泉安彦, 木下慎一,西村和馬, 一村涼夏, 小山豊, 金子周司, 久米利明
    • Organizer
      生体機能と創薬シンポジウム2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 脳の神経細胞の障害とその制御2019

    • Author(s)
      久米利明
    • Organizer
      国際抗老化再生医療学会
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2024-01-30  

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