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A study on the common pathogenesis of Parkinson's disease as a mitochondrial disease

Research Project

Project/Area Number 26293070
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionJuntendo University

Principal Investigator

Imai Yuzuru  順天堂大学, 医学(系)研究科(研究院), 先任准教授 (30321730)

Co-Investigator(Kenkyū-buntansha) 井下 強  順天堂大学, 医学(系)研究科(研究院), 助教 (20601206)
柴 佳保里  順天堂大学, 医学(系)研究科(研究院), 准教授 (30468582)
Co-Investigator(Renkei-kenkyūsha) SHIBA Kahori  順天堂大学, 医学研究科, 准教授 (30468582)
INOSHITA Tsuyoshi  順天堂大学, 医学研究科, 助教 (20601206)
HATTORI Nobutaka  順天堂大学, 医学部, 教授 (80218510)
Research Collaborator MENG Hongrui  順天堂大学, 医学研究科, 研究員 (90736498)
ARANO Taku  順天堂大学, 医学研究科, 研究員 (80750091)
ISHIHAMA Yasushi  京都大学, 薬学研究科, 教授 (30439244)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2015: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywordsミトコンドリア / ドーパミン神経 / iPS細胞 / リン酸化 / PINK1 / Parkin / CHCHD2 / iPS / ドパミン神経 / ショウジョウバエ / パーキンソン病 / ユビキチン / 酸化ストレス / 遺伝学 / シグナル伝達 / 神経変性 / キナーゼ / 神経変性疾患
Outline of Final Research Achievements

The genes for autosomal recessive early-onset Parkinson’s disease, Parkin and PINK1 have been suggested to regulate mitochondrial quality control while the autosomal dominant late-onset Parkinson’s disease gene, CHCHD2, encodes a mitochondrial protein with unknown functions. In this study, we examined the molecular mechanism of the PINK1-Parkin signaling, the molecular functions of CHCHD2 and the relationship between the PINK1-Parkin signaling and CHCHD2 using Drosophila models, iPS cells and mammalian cultured cells.

Report

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

    (57 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (4 results) Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (29 results) (of which Int'l Joint Research: 2 results,  Invited: 6 results) Book (5 results) Remarks (5 results)

  • [Int'l Joint Research] Northwestern University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Northwestern University(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Pennsylvania State University/Max-Planck Institute/Stanford University(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] United Arab Emirates University/Lund University/University of Thrace(アラブ首長国連邦)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Reduced TDP-43 Expression Improves Neuronal Activities in a Drosophila Model of Perry Syndrome2017

    • Author(s)
      Hosaka Y, Inoshita T, Shiba-Fukushima K, Cui C, Arano T, Imai Y, Hattori N
    • Journal Title

      EBioMedicine

      Volume: 21 Pages: 218-227

    • DOI

      10.1016/j.ebiom.2017.06.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of Parkinson's disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c.2017

    • Author(s)
      Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Funayama M, Sato S, Hatta T, Natsume T, Umitsu M, Takagi J, Imai Y, Hattori N.
    • Journal Title

      Nat Commun

      Volume: 8 Issue: 1 Pages: 15500-15500

    • DOI

      10.1038/ncomms15500

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease2017

    • Author(s)
      Shiba-Fukushima Kahori、Ishikawa Kei-Ichi、Inoshita Tsuyoshi、Izawa Nana、Takanashi Masashi、Sato Shigeto、Onodera Osamu、Akamatsu Wado、Okano Hideyuki、Imai Yuzuru、Hattori Nobutaka
    • Journal Title

      Human Molecular Genetics

      Volume: 26 Pages: 3172-3185

    • DOI

      10.1093/hmg/ddx201

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 遺伝子から探るパーキンソン病病態へのミトコンドリアの関与2017

    • Author(s)
      今居 譲、柴佳保里、服部信孝
    • Journal Title

      医学のあゆみ

      Volume: 260 Pages: 85-91

    • Related Report
      2016 Annual Research Report
  • [Journal Article] ミトコンドリア機能障害とパーキンソン病2017

    • Author(s)
      今居 譲
    • Journal Title

      日本臨牀

      Volume: 75 Pages: 28-35

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster.2016

    • Author(s)
      Iyer J, Wang Q, Le T, Pizzo L, Gronke S, Ambegaokar S, Imai Y, Srivastava A, Llamusi Trois B, Mardon G, Artero R, Jackson GR, Isaacs AM, Partridge L, Kumar JP, Girirajan S.
    • Journal Title

      G3

      Volume: - Issue: 5 Pages: 1427-1437

    • DOI

      10.1534/g3.116.027060

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)2016

    • Author(s)
      Klionsky DJ., Abdelmohsen K., Abe A., Abedin MJ.,Inomata M., et al.
    • Journal Title

      Autophagy

      Volume: 12(1) Issue: 1 Pages: 1-222

    • DOI

      10.1080/15548627.2015.1100356

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Generation and characterization of novel conformation-specific monoclonal antibodies for α-synuclein pathology.2015

    • Author(s)
      Vaikath NN, Majbour NK, Paleologou KE, Ardah MT, van Dam E, van de Berg WD, Forrest SL, Parkkinen L, Gai WP, Hattori N, Takanashi M, Lee SJ, Mann DM, Imai Y, Halliday GM, Li JY, El-Agnaf OM.
    • Journal Title

      Neurobiol Dis.

      Volume: 79 Pages: 81-99

    • DOI

      10.1016/j.nbd.2015.04.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Current Topics「PINK1とParkinが紡ぐリン酸化ポリユビキチンの鎖が、Parkinをミトコンドリアへと局在化させる」2015

    • Author(s)
      今居 譲、柴佳保里、服部信孝
    • Journal Title

      実験医学

      Volume: 33 Pages: 940-943

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering.2014

    • Author(s)
      Shiba-Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu KY, Nukina N, Hattori N, Imai Y.
    • Journal Title

      PLoS Genet.

      Volume: 10 Issue: 12 Pages: 1004861-1004861

    • DOI

      10.1371/journal.pgen.1004861

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysine 63-linked polyubiquitination is dispensable for Parkin-mediated mitophagy.2014

    • Author(s)
      Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y.
    • Journal Title

      J Biol Chem.

      Volume: 289 Issue: 48 Pages: 33131-6

    • DOI

      10.1074/jbc.c114.580944

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila.2014

    • Author(s)
      Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y.
    • Journal Title

      PLoS Genet.

      Volume: Jun 5;10(6) Issue: 6 Pages: 1004391-1004391

    • DOI

      10.1371/journal.pgen.1004391

    • Related Report
      2014 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
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ショウジョウバエを用いた遺伝性パーキンソン病の発症機序の研究2014

    • Author(s)
      今居 譲
    • Journal Title

      Aging & Health

      Volume: 23 Pages: 38-41

    • Related Report
      2014 Annual Research Report
  • [Presentation] パーキンソン病類縁疾患ペリー症候群ショウジョウバエモデルのシナプスの異常はTDP-43の減少で軽減される2017

    • Author(s)
      今居 譲
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Reduced TDP-43 expression improves axonal transport and synaptic activity in a Drosophila model of Perry syndrome2017

    • Author(s)
      Hosaka Y, Inoshita T, Cui C, Arano T, Shiba K, Imai Y, Hattori H
    • Organizer
      World Congress of Neurology
    • Related Report
      2017 Annual Research Report
  • [Presentation] PINK1-Parkinシグナル伝達に関与する新規分子の解析2017

    • Author(s)
      柴 佳保里、井下 強、青木 裕子、石濱 泰、今居 譲、服部信孝
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial cristae structure and facilitates cytochrome c release from mitochondria2017

    • Author(s)
      Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Imai Y, Hattori N
    • Organizer
      第40回日本神経学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミトコンドリアの機能を司るパーキンソン病原因遺伝子2017

    • Author(s)
      今居 譲
    • Organizer
      Agilent Technologies XF User Group Meeting Japan
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] パーキンソン病原因遺伝子産物CHCHD2の生理的機能とその変異による病態への関与2017

    • Author(s)
      今居 譲
    • Organizer
      第15回神経科学研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] パーキンソン病原因遺伝子CHCHD2の機能解析2017

    • Author(s)
      今居 譲
    • Organizer
      カテコールアミンと神経疾患研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミトコンドリアの機能維持に関与するパーキンソン病遺伝子の解析2017

    • Author(s)
      今居 譲
    • Organizer
      ミトコンドリア機能研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリアの機能維持に関与するパーキンソン病原因遺伝子の解析2017

    • Author(s)
      今居 譲
    • Organizer
      ミトコンドリア機能研究会
    • Place of Presentation
      大阪市
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c.2016

    • Author(s)
      Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Funayama M, Sato S, Imai Y, Hattori N
    • Organizer
      第39回日本分子生物学会年会 シンポジウム
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] パーキンソン病原因遺伝子によるシナプス小胞動態制御2016

    • Author(s)
      井下 強、荒野 拓、穂坂 有加、孟 紅蕊、梅崎 勇次郎、小杉 紗紀子、森本 高子、小池 正人、Hui-Yun Chang、服部 信孝、今居 譲
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] 小胞輸送と神経分泌を制御するパーキンソン病関連遺伝子のスクリーニング2016

    • Author(s)
      崔 長旭、井下 強、服部 信孝、今居 譲
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson's disease2016

    • Author(s)
      Shiba-Fukushima K, Ishikawa K-I, Takanashi M, Akamatsu W, Imai Y, Hattori N
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] In vivo evidence for the involvement of phospho-ubiquitin signal2016

    • Author(s)
      Shiba-Fukushima K, Ishikawa K-I, Takanashi M, Akamatsu W, Imai Y, Hattori N
    • Organizer
      第39回日本神経学会学術大会
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] Synaptic vesicle dynamics are regulated by a subset of Parkinson’s disease genes2016

    • Author(s)
      Inoshita T, Cui C, Hattori N, Imai Y
    • Organizer
      第39回日本神経学会学術大会
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] CHCHD2, a Parkinson's-Disease Associated Protein, Regulates the Mitochondrial cristae integrity and function in Drosophila2016

    • Author(s)
      Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Imai Y, Hattori N
    • Organizer
      第39回日本神経学会学術大会
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] パーキンソン病新規原因遺伝子CHCHD2の機能解析2016

    • Author(s)
      山下 力、孟 紅蕊、井下強、福嶋佳保里、荒野拓、佐藤栄人、今居譲、服部信孝
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸市
    • Related Report
      2016 Annual Research Report
  • [Presentation] Parkinson's disease-associated mutations of PLA2G6 alters the membrane dynamics.2016

    • Author(s)
      Mori A, Imai Y, Hattori N
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸市
    • Related Report
      2016 Annual Research Report
  • [Presentation] ショウジョウバエ分子遺伝学を利用した遺伝性パーキンソン病へのアプローチ2015

    • Author(s)
      今居 譲
    • 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
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mutations of a mitochondrial protein CHCHD2 in Drosophila lead to Parkinson’s disease-like phenotypes2015

    • Author(s)
      Meng H, Yamashita C, Shiba-Fukushima K, Hattori N, Imai Y
    • Organizer
      Cell Symposia
    • Place of Presentation
      シカゴ
    • Year and Date
      2015-07-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of mitochondrial division and mitophagy by syntaxin 17. Cell Symposia, Multifaceted Mitochondria2015

    • Author(s)
      Arasaki K, Sugo M, Hirota N, Dohmae N, Ortiz-Sandoval C, Simmen T, Imai Y, Hattori N, Tagaya M
    • Organizer
      Cell Symposia
    • Place of Presentation
      シカゴ
    • Year and Date
      2015-07-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phosphorylation of Mitochondrial Polyubiquitin by PINK1 Promotes Parkin Mitochondrial Tethering2015

    • Author(s)
      Shiba-Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, Ryu K-K, Nukina N, Imai Y, Hattori N
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      朱鷺メッセ(新潟県新潟市)
    • Year and Date
      2015-05-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Neurodegenerative mechanism of Parkinson’s disease-associated kinase LRRK22015

    • Author(s)
      Imai Y
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      朱鷺メッセ(新潟県新潟市)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] PINK1によるリン酸化ポリユビキチン鎖のミトコンドリア上での形成は、Parkinのミトコンドリア局在を促す2014

    • Author(s)
      今居 譲
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜)
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Lysine 63-linked polyubiquitination is dispensable for Parkin-mediated mitophagy2014

    • Author(s)
      Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜)
    • Year and Date
      2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mitochondrial quality control by the gene products of early-onset Parkinson's disease2014

    • Author(s)
      今居 譲
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜)
    • Year and Date
      2014-09-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Analysis of sleep-wake rhythms in aged and Parkinson’s disease model flies.2014

    • Author(s)
      Umezaki Y, Yoshii T, Helfrich-Förster C, Tomioka K, Hattori N, Imai Y
    • Organizer
      The 2014 Meeting of the Society for Research on Biological Rhythms.
    • Place of Presentation
      Montana
    • Year and Date
      2014-06-14 – 2014-06-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] PINK1によるParkin機能制御の分子基盤と神経機能への影響2014

    • Author(s)
      今居 譲
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] PINK1-Parkinミトコンドリア品質管理機構に関与する分子の探索2014

    • Author(s)
      柴 佳保里、井下 強、梅崎 勇次郎、今居 譲、服部 信孝
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2014-05-23
    • Related Report
      2014 Annual Research Report
  • [Book] パーキンソン病 -基礎・臨床の最新情報- ミトコンドリア機能障害とパーキンソン病2017

    • Author(s)
      今居 譲
    • Total Pages
      168
    • Publisher
      日本臨床社
    • ISBN
      4910069150171
    • Related Report
      2017 Annual Research Report
  • [Book] Methods Mol Biol.2017

    • Author(s)
      Imai Y, Inoshita T, Shiba-Fukushima K, Meng H, Hattori N
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Nova Biomedical.2017

    • Author(s)
      Inoshita T, Imai Y
    • Total Pages
      225
    • Publisher
      Horizons in Neuroscience Research
    • Related Report
      2016 Annual Research Report
  • [Book] 実験医学2015

    • Author(s)
      今居 譲
    • Publisher
      羊土社
    • Related Report
      2015 Annual Research Report
  • [Book] Cell Death - Autophagy, Necrosis and Apoptosis2015

    • Author(s)
      Arano T, Imai Y
    • Publisher
      InTech
    • Related Report
      2014 Annual Research Report
  • [Remarks] 順天堂大学 脳神経内科紹介

    • URL

      http://www.juntendo-neurology.com/n-kenkyu-syoukai.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 順天堂大学 パーキンソン病病態解明研究講座 紹介

    • URL

      http://www.juntendo-neurology.com/pdf/kenkyu-imai.pdf

    • Related Report
      2015 Annual Research Report
  • [Remarks] 研究紹介

    • URL

      http://www.juntendo-neurology.com/n-kenkyu-syoukai.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] パーキンソン病の2つの原因遺伝子が神経保護する仕組みを解明

    • URL

      http://www.juntendo.ac.jp/graduate/pdf/news14.pdf

    • Related Report
      2014 Annual Research Report
  • [Remarks] パーキンソン病の2つの原因遺伝子の関係についての新たな知見

    • URL

      http://www.juntendo.ac.jp/graduate/pdf/news10.pdf

    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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