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Development of anti-PD chemicals modulating autophagic activity based on lysosomal function

Research Project

Project/Area Number 15H04843
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionJuntendo University

Principal Investigator

Shinji Saiki  順天堂大学, 医学部, 准教授 (00339996)

Co-Investigator(Kenkyū-buntansha) 住吉 克彦  常磐大学, 人間科学部, 准教授 (10445471)
福原 武志  順天堂大学, 医学部, その他 (20359673)
笹澤 有紀子  順天堂大学, 医学部, 学振特別研究員(RPD) (20594922)
古屋 徳彦  順天堂大学, 医学(系)研究科(研究院), 助教 (50401188)
井本 正哉  慶應義塾大学, 理工学部(矢上), 教授 (60213253)
赤松 和土  順天堂大学, 医学(系)研究科(研究院), 特任教授 (60338184)
石川 景一  順天堂大学, 医学部, 非常勤助教 (90733973)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords神経内科学 / オートファジー / リソソーム / パーキンソン病 / 内科 / 脳・神経 / 神経変性 / 神経変性疾患
Outline of Final Research Achievements

In this study, we aim to develop small chemicals for Parkinson's disease therapy by modulating lysosomal functions including its localization control.
First of all, we have identified polyamine metabolites inhibiting mTORC1 activity by lysosomal redistribution without any effects on lysosomal acidification. Also, we detected acetylated polyamine was elevated in serum of Parkinson's disease. I am preparing for a paper submission.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (24 results)

All 2018 2017 2016 2015 Other

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) (of which Int'l Joint Research: 7 results,  Invited: 12 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice.2018

    • Author(s)
      Sato S, Uchihara T, Fukuda T, Noda S, Kondo H, Saiki S, Komatsu M, Uchiyama Y, Tanaka K, Hattori N.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 2813-2813

    • DOI

      10.1038/s41598-018-21325-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum caffeine and metabolites are reliable biomarkers of early Parkinson’s disease.2018

    • Author(s)
      3.Fujimaki M, Saiki S*, Li Y, Kaga N, Taka H, Hatano T, Ishikawa KI, Oji Y, Mori A, Okuzumi A, Koinuma T, Ueno SI, Imamichi Y, Ueno T, Miura Y, Funayama M, Hattori N
    • Journal Title

      Neurology

      Volume: 9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased long-chain acylcarnitines from insufficient β-oxidation as potential early diagnostic markers for Parkinson's disease.2017

    • Author(s)
      Saiki S, Hatano T, Fujimaki M, Ishikawa K, Mori A, Oji Y, Okuzumi A, Fukuhara T, Koinuma T, Nagumo M, Furuya N, Nojiri S, Amo T, Yamashiro K, Hattori N.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 7328-7328

    • DOI

      10.1038/s41598-017-06767-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] パーキンソン病とオートファジー2017

    • Author(s)
      斉木臣二
    • Journal Title

      最新医学

      Volume: 72 Pages: 177-183

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation.2015

    • Author(s)
      Yamada D, Saiki S, Furuya N, Ishikawa K, Imamichi Y, Kambe T, Fujimura T, Ueno T, Koike M, Sumiyoshi K, Hattori N
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 471 Issue: 1 Pages: 109-116

    • DOI

      10.1016/j.bbrc.2016.01.171

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] VPS29-VPS35 intermediate of retromer is stable and may be involved in the retromer complex assembly process.2015

    • Author(s)
      Fuse A, Furuya N, Kakuta S, Inose A, Sato M, Koike M, Saiki S, Hattori N
    • Journal Title

      FEBS Lett.

      Volume: 589 Issue: 13 Pages: 1430-1436

    • DOI

      10.1016/j.febslet.2015.04.040

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Novel autophagy inducers against Parkinson Disease2018

    • Author(s)
      Shinji Saiki
    • Organizer
      The 8th International Symposium on Autophagy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Metabolomics and Parkinson’s disease and related disorders2018

    • Author(s)
      Shinji Saiki
    • Organizer
      Takamatsu International Symposium for PD and MD in Tokyo
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of plasma metabolite biomarker for Parkinson’s disease2018

    • Author(s)
      Shinji Saiki
    • Organizer
      RIKEN Young Researcher Workshop
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] オートファジー制御によるパーキンソン病治療薬探索2017

    • Author(s)
      斉木臣二
    • Organizer
      オートファジー合同セミナー
    • Place of Presentation
      セレクトン福島
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] オートファジーを標的としたパーキンソン病治療薬開発2017

    • Author(s)
      斉木臣二
    • Organizer
      日経バイオテク プロフェッショナルセミナー
    • Place of Presentation
      Learning Square新橋
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Autophagy and mitophagy regulation by small chemicals2016

    • Author(s)
      Shinji Saiki
    • Organizer
      The 13th Conference of Asian Society for Mitochondrial Research and Medicine
    • Place of Presentation
      Shinagawa
    • Year and Date
      2016-10-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Blood biomarkers for Parkinson’s disease2016

    • Author(s)
      Shinji Saiki
    • Organizer
      第57回日本神経学会
    • Place of Presentation
      神戸国際会館、神戸市、兵庫県
    • Year and Date
      2016-05-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Drug development for Parkinson’s disease and autophagy2016

    • Author(s)
      Shinji Saiki
    • Organizer
      The 4th Sino-Japan Symposium on Autophagy
    • Place of Presentation
      Beijing
    • Year and Date
      2016-04-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Drug development for Parkinson's disease and autophagy2016

    • Author(s)
      Shinji Saiki
    • Organizer
      The 4th Sino-Japan Symposium on Autophagy
    • Place of Presentation
      Chinese Academy of Sciences, Beijing, China
    • Year and Date
      2016-04-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] オートファジー調節による神経変性疾患の治療戦略2016

    • Author(s)
      斉木臣二
    • Organizer
      AMED難治性疾患実用化研究事業『筋萎縮性側索硬化症の新規治療法開発を目指した病態解明』平成28年度ワークショップ
    • Place of Presentation
      東京都市センターホテル
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Plasma Biomarkers for Parkinson’s disease.2015

    • Author(s)
      Shinji Saiki
    • Organizer
      XXI World Congress on Parkinson’s disease and related disorders
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2015-12-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] パーキンソン病分子病態解析に基づくオートファジー促進小分子化合物の同定2015

    • Author(s)
      斉木臣二
    • Organizer
      第9回オートファジー研究会
    • Place of Presentation
      淡路夢舞台国際会議場、淡路市、兵庫県
    • Year and Date
      2015-11-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] Clinical Neuroscience2015

    • Author(s)
      斉木臣二
    • Total Pages
      130
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report
  • [Book] Parkinson's disease and Movement Disorders, 6th edition2015

    • Author(s)
      Shinji Saiki
    • Total Pages
      644
    • Publisher
      Lippincott Williams and Wilkins
    • Related Report
      2015 Annual Research Report
  • [Remarks] 化合物による治療探索研究・オートファジー関連研究

    • URL

      http://www.juntendo-neurology.com/pdf/saiki2015.pdf

    • Related Report
      2017 Annual Research Report 2015 Annual Research Report
  • [Remarks] 斉木臣二・古屋徳彦グループ(研究紹介)

    • URL

      http://www.juntendo-neurology.com/pdf/saiki2015.pdf

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] パーキンソン病の重症度判定方法2016

    • Inventor(s)
      斉木臣二 他
    • Industrial Property Rights Holder
      斉木臣二 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Acquisition Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] パーキンソン病診断指標2016

    • Inventor(s)
      服部信孝、斉木臣二ら
    • Industrial Property Rights Holder
      服部信孝、斉木臣二ら
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-02-02
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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