• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Generation of the novel mouse model for Parkinson's disease derived from two-hit hypothesis

Research Project

Project/Area Number 25461291
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionJuntendo University

Principal Investigator

Funayama Manabu  順天堂大学, 医学部, 准教授 (70468578)

Co-Investigator(Renkei-kenkyūsha) AMO Taku  防衛大学校, 応用化学科, 助教 (40453922)
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: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsミトコンドリア / パーキンソン病 / 電子伝達系 / 呼吸鎖複合体 / 感受性遺伝子 / CHCHD2 / 複合体IV / CRSPR/Cas9 / ノックインマウス / NDUFV2 / MPTP / iTRAQ / モデル動物
Outline of Final Research Achievements

To identify the molecules related vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity of NDUFV2 heterozygous knockout mice, I performed high throughput molecular profiling using isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. A total of 17 proteins were identified as statistically different between wild-type and NDUFV2 heterozygous knockout mice in the midbrain of 48 hours after the MPTP administration. This results raise the possibility of discovering novel proteins related the pathogenesis of Parkinson’s disease (PD).
To analyze molecular phenotypes of CHCHD2, which have been reported as a novel causative gene for autosomal dominant PD, I generated CHCHD2 knockout SH-SY5Y cells using CRISPR-Cas9 system. CHCHD2 knockout SH-SY5Y cell was markedly decreased protein levels and activity of cytochrome c oxidase (Complex IV).

Report

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

    (32 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (6 results) Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Acknowledgement Compliant: 1 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] メイヨークリニック, ジャクソンビル/ノースショア大学/スタンフォード大学(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] テュービンゲン大学/リューベック大学/マックス・プランク研究所(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] ブリティッシュコロンビア大学/トロント大学/オタワ大学(カナダ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] ルクセンブルク大学(ルクセンブルク)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] パリ大学(フランス)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2015 Annual Research Report
  • [Journal Article] FBXO7 mutations in Parkinson's disease and multiple system atrophy.2016

    • Author(s)
      Conedera S, Apaydin H, Li Y, et al.
    • Journal Title

      Neurobiol Aging.

      Volume: 40 Pages: 192.e1-192.e5

    • DOI

      10.1016/j.neurobiolaging.2016.01.003

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication.2016

    • Author(s)
      Takamura S, Ikeda A, Nishioka K, Furuya H, Tashiro M, Matsushima T, Li Y, Yoshino H, Funayama M, Morinobu S, Hattori N.
    • Journal Title

      Parkinsonism Relat Disord.

      Volume: S1353-8020 Pages: 30028-1

    • DOI

      10.1016/j.parkreldis.2016.01.028

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CHCHD2 and Parkinson's disease-Authors' reply.2015

    • Author(s)
      Funayama M, Hattori N.
    • Journal Title

      Lancet Neurology

      Volume: 14 Issue: 7 Pages: 682-683

    • DOI

      10.1016/s1474-4422(15)00097-6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders.2015

    • Author(s)
      Ogaki K, Koga S, Heckman MG, et al.
    • Journal Title

      Neurology

      Volume: 85 Issue: 23 Pages: 2016-2025

    • DOI

      10.1212/wnl.0000000000002170

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout.2015

    • Author(s)
      Matsuo H, Tomiyama H, Satake W, Chiba T, Onoue H, Kawamura Y, Nakayama A, ShimizuS, Sakiyama M, Funayama M, Nishioka K, Shimizu T, Kaida K, Kamakura K, Toda T, Hattori N, ShinomiyaN.
    • Journal Title

      Ann Clin Transl Neurol

      Volume: 2 Issue: 3 Pages: 302-306

    • DOI

      10.1002/acn3.167

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus2015

    • Author(s)
      Rubio ME, Fukazawa Y, Kamasawa N, Clarkson C, Molnar E, Shigemoto R
    • Journal Title

      J Comp Neurol

      Volume: 588 Pages: 29-35

    • DOI

      10.1016/j.neulet.2014.12.052

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2014 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a Japanese family with LRRK2 p.R1441G-related Parkinson's disease.2014

    • Author(s)
      Hatano T, Funayama M, Kubo S, Mata IF, Oji Y, Mori A, Zabetian CP, Waldherr SM, Yoshino H, Oyama G, Shimo Y, Fujimoto K, Oshima H, Kunii Y, Yabe H, Mizuno Y, Hattori N.
    • Journal Title

      Neurobiol Aging.

      Volume: Nov;35(11) Issue: 11 Pages: 2656.e17-2656.e23

    • DOI

      10.1016/j.neurobiolaging.2014.05.025

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] EIF4G1 gene mutations are not a common cause of Parkinson's disease in the Japanese population2014

    • Author(s)
      Nishioka K, Funayama M, Vilarino-GuellC, Ogaki K, Li Y, Sasaki R, Kokubo Y, Kuzuhara S, Kachergus JM, Cobb SA, Takahashi H, Mizuno Y, Farrer MJ, Ross OA, Hattori N
    • Journal Title

      Parkinsonism Relat Disord.

      Volume: 20 Issue: 6 Pages: 659-61

    • DOI

      10.1016/j.parkreldis.2014.03.004

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Juvenile-onset parkinsonism with digenic parkin and PINK1 mutations treated with subthalamic nucleus stimulation at 45 years after disease onset.2014

    • Author(s)
      Nakahara K, Ueda M, Yamada K, Koide T, Yoshimochi G, Funayama M, Kim JH, Yamakawa S, Mori A, Misumi Y, Uyama E, Hattori N, Ando Y.
    • Journal Title

      J Neurol Sci.

      Volume: 15 Issue: 1-2 Pages: 276-277

    • DOI

      10.1016/j.jns.2014.07.053

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease.2014

    • Author(s)
      Li Y, Sekine T, Funayama M, Li L, Yoshino H, Nishioka K, Tomiyama H, Hattori N
    • Journal Title

      Neurobiol Aging.

      Volume: 35 Issue: 4 Pages: 935.e3-935.e8

    • DOI

      10.1016/j.neurobiolaging.2013.09.019

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The evaluation of polyglutamine repeats in autosomal dominant Parkinson's disease.2014

    • Author(s)
      Yamashita C, Tomiyama H, Funayama M, Inamizu S, Ando M, Li Y, Yoshino H, Araki T, Ichikawa T, Ehara Y, Ishikawa K, Mizusawa H, Hattori N.
    • Journal Title

      Neurobiol Aging.

      Volume: 35 Issue: 7 Pages: 1779.e17-1779.e21

    • DOI

      10.1016/j.neurobiolaging.2014.01.022

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, andCBS2013

    • Author(s)
      Ogaki K
    • Journal Title

      Parkinsonism & Related Disorders

      Volume: 19 Issue: 1 Pages: 15-20

    • DOI

      10.1016/j.parkreldis.2012.06.019

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] ATP13A2 deficiency induces a decrease in cathepsin D activity, fingerprint-like inclusion body formation, and selective degeneration of dopaminergic neurons.2013

    • Author(s)
      Matsui H, Sato F, Sato S, Koike M, Taruno Y, Saiki S, Funayama M, Ito H, Taniguchi Y, Uemura N, Toyoda A, Sakaki Y, Takeda S, Uchiyama Y, Hattori N, Takahashi R.
    • Journal Title

      FEBS Lett

      Volume: 587(9) Issue: 9 Pages: 1316-1325

    • DOI

      10.1016/j.febslet.2013.02.046

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Keeping Up with New Genetic Predispositions and Mutations in Parkinson’s Disease2016

    • Author(s)
      Funayama M, Hattori N
    • Organizer
      5th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress
    • Place of Presentation
      マニラ、フィリピン
    • Year and Date
      2016-03-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CHCHD2は家族性パーキンソン病の新規原因遺伝子である2015

    • Author(s)
      舩山 学、服部 信孝
    • Organizer
      第9回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      東京都品川区
    • Year and Date
      2015-10-15
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] CHCHD2 is novel gene for autosomal dominant Parkinson's disease2015

    • Author(s)
      Funayama M, Hattori N
    • Organizer
      10th Annual GEoPD Meeting in Tokyo
    • Place of Presentation
      東京都港区
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Genetics of PD2015

    • Author(s)
      Funayama M
    • Organizer
      Basic Scientists Summer School, Tokyo, Japan
    • Place of Presentation
      東京都千代田区
    • Year and Date
      2015-08-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CHCHD2は家族性パーキンソン病の新規原因遺伝子である2015

    • Author(s)
      舩山 学
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      新潟県新潟市
    • Year and Date
      2015-05-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] ミトコンドリア呼吸鎖複合体に着目した新規パーキンソン病モデルマウスの解析.2014

    • Author(s)
      舩山 学, 服部 信孝.
    • Organizer
      第55回日本神経病理学会総会学術研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-06-06
    • Related Report
      2014 Research-status Report
  • [Presentation] A screening of neuroprotective compounds for Parkinson’s disease from herbal medicines.2013

    • Author(s)
      Yamada D, Fujimaki T, Saiki S, Tashiro E, Funayama M, Imoto M, Hattori N.
    • Organizer
      International Symposium on Mitochondria 2013
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 日本人パーキンソン病におけるVPS35 D620N変異の同定.2013

    • Author(s)
      舩山学、安藤真矢、李元哲、柏原健一、村上善勇、石津暢隆、豊田千純子、野口克彦、橋本貴司、中野直樹、佐々木良元、小久保康昌、葛原茂樹、大垣光太郎、山下力、吉野浩代、波田野琢、富山弘幸、服部信孝.
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] 別冊 日本臨床 新領域別症候群シリーズ No.27、神経症候群(第2版)(II) -その他の神経疾患を含めて-2014

    • Author(s)
      舩山 学、安藤真矢、服部信孝
    • Total Pages
      903
    • Publisher
      日本臨床社
    • Related Report
      2013 Research-status Report
  • [Remarks] 遺伝性パーキンソン病の集学的研究 ~分子遺伝学的アプローチからの解明を目指す~

    • URL

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

    • Related Report
      2015 Annual Research Report
  • [Remarks] 遺伝性パーキンソン病の原因遺伝子を新たに発見

    • URL

      http://www.juntendo.ac.jp/graduate/pdf/news15.pdf

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2022-02-01  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi