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Development of autophagy enhancing chemicals based on Parkinson's disease pathogenesis.

Planned Research

Project AreaMultidisciplinary research on autophagy: from molecular mechanisms to disease states
Project/Area Number 25111007
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionJuntendo University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 佐藤 栄人  順天堂大学, 医学部, 准教授 (00445537)
Co-Investigator(Renkei-kenkyūsha) IMOTO Masaya  慶應義塾大学, 理工学部, 教授 (60213253)
HATTORI Nobutaka  順天堂大学, 医学部, 教授 (80218510)
Research Collaborator FUNAYAMA Manabu  順天堂大学, 医学部, 准教授 (70468578)
ISHIKAWA Kei-ichi  順天堂大学, 医学部, 非常勤助教 (90733973)
FURUYA Norihiko  順天堂大学, 医学部, 助教 (50401188)
SASAZAWA Yukiko  日本学術振興会, 特別研究員(RPD) (20594922)
YAMADA Daisuke  順天堂大学, 医学部, 助教 (30757539)
Project Period (FY) 2013-06-28 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥105,430,000 (Direct Cost: ¥81,100,000、Indirect Cost: ¥24,330,000)
Fiscal Year 2017: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2016: ¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
Fiscal Year 2015: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2014: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2013: ¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000)
Keywordsオートファジー / 神経内科学 / ケミカルバイオロジー / パーキンソン病 / マイトファジー / 内科 / 脳・神経 / 創薬シーズ / リソソーム / 蛋白分解 / 小分子化合物 / 神経変性疾患
Outline of Final Research Achievements

According to mutation screening of the WDR45 gene responsible for SENDA, we identified high prevalence of the disease in patients with characteristic phenotype.
We revealed that Dynactin mutant, with pathogenic mutant of Perry syndrome, one of the parkinsonian disorders, has inhibiting effect on autophagic flux by decreased autophagosome-lysosome fusion step, resulting in apoptosis. Also, CHCHD2, a novel gene responsible for autosomal dominant Parkinson's disease, was identified and now its molecular function is investigated within the mitochondria. Using TH neurons selective autophagy deficient mice, intraneuronal inclusions have been detected in the affected lesions.

Report

(6 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (45 results)

All 2018 2017 2016 2015 2014 2013 Other

All Journal Article (11 results) (of which Peer Reviewed: 10 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (23 results) (of which Int'l Joint Research: 7 results,  Invited: 20 results) Book (3 results) Remarks (4 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 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 disease2018

    • Author(s)
      Motoki Fujimaki, Shinji Saiki, Yuanzhe Li, Naoko Kaga, Taku Hatano, Kei-Ichi Ishikawa, Yutaka Oji, Akio Mori, Ayami Okuzumi, Takahiro Koinuma, Shin-Ichi Ueno, Yoko Imamichi, Takashi Ueno, Yoshiki Miura, Manabu Funayama
    • Journal Title

      Neurology

      Volume: 90

    • 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] Identification of novel biomarkers for Parkinson's disease by metabolomic technologies.2015

    • Author(s)
      Hatano T, Saiki S, Okuzumi A, Mohney RP, Hattori N.
    • Journal Title

      J Neurol Neurosurg Psychiatry.

      Volume: jnnp-2014 Issue: 3 Pages: 2014-309676

    • DOI

      10.1136/jnnp-2014-309676

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [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
  • [Journal Article] High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism.2015

    • Author(s)
      Nishioka K, Oyama G, Yoshino H, Li Y, Matsushima T, Takeuchi C, Mochizuki Y, Mori-Yoshimura M, Murata M, Yamasita C, Nakamura N, Konishi Y, Ohi K, Ichikawa K, Terada T, Obi T, Funayama M, Saiki S, Hattori N.
    • Journal Title

      Neurobiol Aging.

      Volume: S0197 Issue: 5 Pages: 54-58

    • DOI

      10.1016/j.neurobiolaging.2015.01.020

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study.2015

    • Author(s)
      Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Yuanzhe L, Ogaki K, Ando M, Yoshinon H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N.
    • Journal Title

      Lancet Neurol

      Volume: 14 Issue: 3 Pages: 274-282

    • DOI

      10.1016/s1474-4422(14)70266-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] P150glued-associated disorders are caused by activation of intrinsic apoptotic pathway.2014

    • Author(s)
      Ishikawa K, Saiki S, Furuya N, Yamada D, Imamichi Y, Li Y, Kawajiri S, Sasaki H, Koike M, Tsuboi Y, Hattori N.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 4 Pages: e94645-e94645

    • DOI

      10.1371/journal.pone.0094645

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation by mitophagy2014

    • Author(s)
      Hattori N, Saiki S, Imai Y.
    • Journal Title

      Int J Biochem Cell Biol.

      Volume: 53 Pages: 147-50

    • DOI

      10.1016/j.biocel.2014.05.012

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] 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] 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
      日本学術振興会A3事業 日本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
      神戸国際会議場、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
      Institute of Biophysics, 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
  • [Presentation] オートファジーとパーキンソン病病態2015

    • Author(s)
      斉木臣二
    • Organizer
      第45回(2015)新潟神経学夏期セミナー
    • Place of Presentation
      新潟大学脳研究所統合脳機能研究センター
    • Year and Date
      2015-07-23 – 2015-07-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] PINK1/parkin-mediated mitophagy and apoptosis.2014

    • Author(s)
      Shinji Saiki
    • Organizer
      第16回北東アジアシンポジウム
    • Place of Presentation
      Westin Chosun Hotel、釜山、韓国
    • Year and Date
      2014-12-18 – 2014-12-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] オートファジー調節作用を持つ薬剤の探索 -既存薬ライブラリーを用いて-2014

    • Author(s)
      平野一興、斉木臣二、古屋徳彦、山田大介、石川景一、佐谷秀行、服部信孝
    • Organizer
      厚生労働科学研究委託事業 難治性疾患等克服研究事業 「パーキンソン病患者由来iPS細胞を中心とする多面的疾患モデルに立脚した革新的医薬品の開発」 第2回班会議
    • Place of Presentation
      順天堂大学10号館1階会議室、東京
    • Year and Date
      2014-12-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] PD患者におけるオートファジー関連BM同定の試み2014

    • Author(s)
      斉木臣二
    • Organizer
      第8回オートファジー研究会
    • Place of Presentation
      シャトレーゼ ガトーキングダム サッポロ北海道、札幌
    • Year and Date
      2014-11-09 – 2014-11-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 抗結核薬エタンブトールのオートファジー阻害作用2014

    • Author(s)
      山田大介, 斉木臣二, 古屋徳彦, 石川景一, 今道洋子, 神戸大朋, 藤村 務, 上野隆, 小池正人, 服部信孝
    • Organizer
      第8回オートファジー研究会
    • Place of Presentation
      シャトレーゼ ガトーキングダム サッポロ北海道、札幌
    • Year and Date
      2014-11-09 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] パーキンソン病とオートファジー2014

    • Author(s)
      斉木臣二
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館、京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] パーキンソン病と慢性炎症2014

    • Author(s)
      斉木臣二
    • Organizer
      第55回日本神経学会総会 シンポジウム31
    • Place of Presentation
      福岡国際会議場等
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ペリー症候群の分子病態とアポトーシスの関係2014

    • Author(s)
      石川景一, 斉木臣二, 古屋徳彦, 山田大介, 今道洋子, 李元哲, 河尻澄宏, 佐々木寛典, 小池正人, 坪井義夫,服部信孝
    • Organizer
      カテコールアミンと神経疾患研究会 2014
    • Place of Presentation
      品川プリンスホテル
    • Year and Date
      2014-04-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] オートファジーを標的としたパーキンソン病治療について2013

    • Author(s)
      斉木臣二
    • Organizer
      第7回オートファジー研究会
    • Place of Presentation
      ヤマハリゾート嬬恋 静岡県
    • Year and Date
      2013-12-19 – 2013-12-21
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] パーキンソン病病態とオートファジーの関連について2013

    • Author(s)
      斉木臣二
    • Organizer
      文部科学省新学術領域「細胞内ロジスティクス」シンポジウム
    • Place of Presentation
      淡路夢舞台国際会議場
    • Year and Date
      2013-09-17 – 2013-09-18
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] パーキンソン病の臨床と創薬 -オートファジーとの関連を中心に-2013

    • Author(s)
      斉木臣二
    • Organizer
      第33回ゲノム創薬フォーラム
    • Place of Presentation
      東京大学医科学研究所
    • Year and Date
      2013-07-25
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] Methods in Molecular Biology, Mitophagy2017

    • Author(s)
      Shinji Saiki, Nobutaka Hattori
    • Total Pages
      200
    • Publisher
      Splinger
    • Related Report
      2017 Annual Research Report
  • [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
  • [Remarks] 研究紹介 斉木臣二・古屋徳彦グループ

    • URL

      http://www.juntendo-neurology.com/pdf/kenkyu-saeki-furuya.pdf

    • Related Report
      2014 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/kenkyu-saeki-furuya.pdf

    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] オートファジー誘導剤2017

    • Inventor(s)
      斉木臣二、他
    • Industrial Property Rights Holder
      斉木臣二、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 化合物又はその塩、及びパーキンソン病治療薬又は予防薬2017

    • Inventor(s)
      井本正哉、斉木臣二、他
    • Industrial Property Rights Holder
      井本正哉、斉木臣二、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Acquisition Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [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)] パーキンソン病の重症度判定方法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
      2016-10-27
    • Related Report
      2016 Annual Research Report

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Published: 2013-07-10   Modified: 2019-03-29  

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