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Study of oxydative stress sensor DJ-1 for therapeutic target of neurodegenerative diseases

Research Project

Project/Area Number 25460109
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionRitsumeikan University (2015)
Kyoto Pharmaceutical University (2013-2014)

Principal Investigator

Kitamura Yoshihisa  立命館大学, 薬学部, 教授 (60195295)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsDJ-1タンパク質 / DJ-1結合化合物 / パーキンソン病 / アルツハイマー病 / 神経変性疾患 / 抗酸化作用 / ニコチン受容体 / DJ-1結合タンパク質 / 神経保護 / 神経再生 / 多能性幹細胞
Outline of Final Research Achievements

Oxidative stress is one of the causes of neurodegenerative diseases, such as Parkinson's (PD) and Alzheimer's diseases (AD). Since symptomatic disease therapies are used, identification of compounds or proteins that inhibit oxidative stress-induced neuronal cell death is necessary. DJ-1 is a causative gene product of familial PD and plays a role in anti-oxidative stress reaction. Recently, we have identified some DJ-1-binding compounds. In this study, wild-type and DJ-1-knockout mice were injected intraperitoneally with DJ-1-binding compounds in the presence or absencs of neurotoxin MPTP. This research showed that DJ-1-binding compounds inhibited MPTP-induced reduction of retention time on the rotor rod bar, neuronal cell death in the substantia nigra and striatum and dopamine content in wild-type mice but not in DJ-1-knockout mice. From these results suggest that DJ-1 is one of novel therapeutic molecular targets for neurodegenerative diseases.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (21 results)

All 2016 2015 2014 2013 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (10 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Inhibition of monocarboxylate transporter 1 suppresses the proliferation of glioblastoma stem cells.2016

    • Author(s)
      Takada T, Takata K, Ashihara E.
    • Journal Title

      J Physiol Sci

      Volume: 66 Pages: 74-81

    • DOI

      10.1016/j.neuint.2016.02.008

    • NAID

      40020922534

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DJ-1-dependent protective activity of DJ-1-binding compound no. 23 against neuronal cell death in MPTP-treated mouse model of Parkinson's disease.2015

    • Author(s)
      Takahashi-Niki K., Inafune A., Michitani N., Hatakeyama Y., Suzuki K., Sasaki M., Kitamura Y., Niki T, Iguchi-Ariga S.M., Ariga H..
    • Journal Title

      J. Pharmacol. Sci.

      Volume: 127 Issue: 3 Pages: 305-310

    • DOI

      10.1016/j.jphs.2015.01.010

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Temporal Changes of CD68 and α7 Nicotinic Acetylcholine Receptor Expression in Microglia in Alzheimer’s Disease-Like Mouse Models2015

    • Author(s)
      Akihiro Matsumura, Syuuichirou Suzuki, Naotoshi Iwahara, Shin Hisahara, Jun Kawamata, Hiromi Suzuki, Ayano Yamauchi, Kazuyuki Takata, Yoshihisa Kitamura and Shun Shimohama
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 44 Issue: 2 Pages: 409-423

    • DOI

      10.3233/jad-141572

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of oxidative stress on the solubility of HRD1, a ubiquitin ligase implicated in Alzheimer's disease.2014

    • Author(s)
      Ryo Saito, Masayuki Kaneko, Yoshihisa Kitamura, Kazuyuki Takata, Koichi Kawada, Yasunobu Okuma, and Yasuyuki Nomura
    • Journal Title

      PLoS One

      Volume: 9 (5)

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacological assessment of methamphetamine-induced behavioral hyperactivity mediated by dopaminergic transmission in planarian Dugesia japonica.2014

    • Author(s)
      Natsuka Tashiro, Kaneyasu Nishimura, Kanako Daido, Tomoe Oka, Mio Todo, Asami Toshikawa, Jun Tsushima, Kazuyuki Takata, Kanji Yoshimoto, Kiyokazu Agata, and Yoshihisa Kitamura
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 449 (4) Pages: 412-418

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Therapeutic effects of human mesenchymal and hematopoietic stem cells on rotenone-treated parkinsonian mice2013

    • Author(s)
      Inden M, Takata K, Nishimura K, Kitamura Y, Ashihara E, Yoshimoto K, Ariga H, Honmou O, Shimohama S
    • Journal Title

      Journal of Neuroscience Research

      Volume: 91 Issue: 1 Pages: 62-72

    • DOI

      10.1002/jnr.23128

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 3-[(2,4-Dimethoxy)benzylidene]-anabasei nedihydrochloride protects against 6-hydroxydopamine-induced parkinsonian neurodegeneration through α7 nicotinic acetylcholine receptor stimulation in rats2013

    • Author(s)
      Suzuki S, Kawamata J, Matsushita T, Matsumura A, Hisahara S, Takata K, Kitamura Y, Kem W, Shimohama S
    • Journal Title

      J Neurosci Res.

      Volume: 91(3) Issue: 3 Pages: 462-71

    • DOI

      10.1002/jnr.23160

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] パーキンソン病モデルにおけるガランタミンのニコチン受容体を介した薬物旋回運動.2015

    • Author(s)
      位田雅俊,北村佳久,下濱俊
    • Organizer
      第127回日本薬理学会近畿部会
    • Place of Presentation
      長良川国際会議場 (岐阜県、岐阜市)
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 由来がん細胞へホーミングするglioblastoma由来エクソソームの解析〜がん標的化技術応用のための指向性決定因子の探索〜2014

    • Author(s)
      戸田侑紀、高田和幸、中川由布子、川上光、藤岡周助、小林数也、服部恭尚、北村佳久、赤路健一、芦原英司
    • Organizer
      第64回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] アルツハイマー病の細胞治療法の開発を目指した、骨髄由来細胞、ミクログリアおよびマクロファージの定性・機能解析2014

    • Author(s)
      河西翔平、高田和幸、黒田絵莉子、杉野友紀、北村佳久、芦原英司
    • Organizer
      第64回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Wnt/β-catenin 経路阻害化合物のスクリーニング系の構築2014

    • Author(s)
      若林亮介、高田和幸、中村誠宏、大矢博己、菅 倫子、川幡尚平、福田浩紀、赤路健一、松田久司、北村佳久、芦原英司
    • Organizer
      第64回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Cancer cell tropism of glioblastoma-derived exosomes regulated by their lipid components.2014

    • Author(s)
      Yuki Toda, Kazuyuki Takata, Yuko Nakagawa, Hikaru Kawakami, Shusuke Fujioka, Kazuya Kobayashi, Yasunao Hattori, Yoshihisa Kitamura, Kenichi Akaji, and Eishi Ashihara
    • Organizer
      FEBS EMBO 2014
    • Place of Presentation
      Paris, France
    • Year and Date
      2014-08-30 – 2014-09-04
    • Related Report
      2014 Research-status Report
  • [Presentation] がん細胞選択的ドラッグデリバリー応用を目的としたエクソソームの脂質組成解析2014

    • Author(s)
      戸田侑紀、高田和幸、中川由布子、川上光、藤岡周助、小林数也、服部恭尚、北村佳久、赤路健一、芦原英司
    • Organizer
      第6回日本RNAi研究会
    • Place of Presentation
      広島
    • Year and Date
      2014-08-28 – 2014-08-30
    • Related Report
      2014 Research-status Report
  • [Presentation] パーキンソン病モデルマウスにおけるヒト由来幹細胞の神経保護作用2014

    • Author(s)
      北村佳久、高田和幸、下濱 俊、芦原英司
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] アルツハイマー病の細胞治療法開発に向けた骨髄由来細胞のAβ貪食機能と内在性ミクログリアへの作用解析2014

    • Author(s)
      杜氏裕美子、高田和幸、河西翔平、高田哲也、北村佳久、下濱 俊、芦原英司
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] アルツハイマー病治療薬リバスチグミンの神経機能改善に関する解析2013

    • Author(s)
      富永 淳、高田和幸、太田垣健人、松井香保里、池上倫代、弓倉 梓、北村佳久、下濱 俊、芦原英司
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2013
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] リバスチグミンの神経保護作用機序ならびに認知機能障害改善作用の解析2013

    • Author(s)
      高田和幸、北村佳久、金井美乃里、太田垣健人、富永 淳、松井香保里、弓倉 梓、芦原英司、下濱 俊
    • Organizer
      第32回日本認知症学会学術集会
    • Place of Presentation
      松本
    • Related Report
      2013 Research-status Report
  • [Book] Development of cell therapeutic strategies for Alzheimer’s disease using animal models. In: Animal Models in Human Disease: Applications, Outcomes and Controversies (Ed. S.A. Murray)2013

    • Author(s)
      Kazuyuki Takata, Shohei Kawanishi, Yumiko Touji, Tetsuya Takada, Yoshihisa Kitamura, and Eishi Ashihara
    • Publisher
      NOVA Science Publishers
    • Related Report
      2013 Research-status Report
  • [Book] A survey of the molecular basis for the generation of functional dopaminergic neurons from pluripotent stem cells: Insights from regenerative biology and regenerative medicine. In: Neural Stem Cells (Ed. L. Bonfanti)2013

    • Author(s)
      Kaneyasu Nishimura, Yoshihisa Kitamura, Kiyokazu Agata, and Jun Takahashi
    • Publisher
      InTech Europe
    • Related Report
      2013 Research-status Report
  • [Remarks] 研究概要・研究業績一覧

    • URL

      http://research-db.ritsumei.ac.jp/Profiles/118/0011784/profile.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 「パーキンソン病」の創薬に向けた研究、「アルツハイマー病」の新規治療戦略の開発

    • URL

      http://labo.kyoto-phu.ac.jp/seiri/pg136.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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