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Exploring the pathomechanism of Pakinson's disease by novel alpha-synuclein transgenic mice

Research Project

Project/Area Number 24790879
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionKyoto University

Principal Investigator

YAMAKADO HODAKA  京都大学, 医学(系)研究科(研究院), 助教 (10378771)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsパーキンソン病
Research Abstract

We created the alpha-synuclein BAC transgenic mice and rats harboring alpha-syn gene and its expression regulatory regions. To obtain symptomatic model, we introduced A53T mutation, risk SNPs and modified Rep1 region to alpja-syn BAC clone by Ret/ET recombination system. Now we are analyzing these transgenic animals, and speculates alpha-syn BAC Tg mice/rats crossed with glucocerebrosidase mutant are promising animal model for PD.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (50 results)

All 2014 2013 2012 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 3 results) Presentation (28 results) Book (5 results) Remarks (1 results)

  • [Journal Article] Exploring the Pathogenetic Mechanisms underlying Parkinson's Disease in Medaka Fish.2014

    • Author(s)
      Matsui H, Uemura N, Yamakado H, Takeda S, Takahashi R
    • Journal Title

      J Parkinsons Dis

      Volume: 4 Issue: 2 Pages: 301-310

    • DOI

      10.3233/jpd-130289

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploring the Pathogenetic Mechanisms underlying Parkinson's Disease in Medaka Fish2013

    • Author(s)
      Matsui H, Uemura N, Yamakado H, Takeda S, Takahashi R
    • Journal Title

      J Parkinsons Dis.

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The function of parkin : revisited2013

    • Author(s)
      Yamakado H, Takahashi R
    • Journal Title

      Mov Disord.

      Volume: 14 Pages: 1936-1936

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic correction will be a standard method for the patient-derived ips cell research?2013

    • Author(s)
      Takahashi R, Yamakado H
    • Journal Title

      Mov Disord.

      Volume: 14 Pages: 1935-1935

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chicken DT40 cell line lacking DJ-1, the gene responsible for familial Parkinson's disease, displays mitochondrial dysfunction2013

    • Author(s)
      Minakawa EN, Yamakado H, Tanaka A, Uemura K, Takeda S, Takahashi R
    • Journal Title

      Neurosci Res.

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice2013

    • Author(s)
      Ageta-Ishihara N, Yamakado H, Morita T, Hattori S, Takao K, Miyakawa T, Takahashi R, Kinoshita M
    • Journal Title

      Mol Brain

      Volume: 6 Pages: 35-35

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] PINK1 and Parkin complementarily protect dopaminergic neurons in vertebrates2013

    • Author(s)
      Matsui H, Gavinio R, Asano T, Uemura N, Ito H, Taniguchi Y, Kobayashi Y, Maki T, Shen J, Takeda S, Uemura K, Yamakado H, Takahashi R
    • Journal Title

      Hum Mol Genet.

      Volume: 22 Pages: 2423-34

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats2013

    • Author(s)
      Nuber S, Harmuth F, Kohl Z, Adame A, Trejo M, Schonig K, Zimmermann F, Bauer C, Casadei N, Giel C, Calaminus C, Pichler BJ, Jensen PH, Muller CP, Amato D, Kornhuber J, Teismann P, Yamakado H, Takahashi R, Winkler J, Masliah E, Riess O
    • Journal Title

      Brain

      Volume: 136 Pages: 412-32

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The function of parkin: revisited.2013

    • Author(s)
      Yamakado H, Takahashi R.
    • Journal Title

      Mov Disord.

      Volume: 28(14) Issue: 14 Pages: 1936-1936

    • DOI

      10.1002/mds.25711

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic correction will be a standard method for the patient-derived ips cell research?2013

    • Author(s)
      Takahashi R, Yamakado H.
    • Journal Title

      Mov Disord.

      Volume: 28(14) Issue: 14 Pages: 1935-1935

    • DOI

      10.1002/mds.25710

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chicken DT40 cell line lacking DJ-1, the gene responsible for familial Parkinson's disease, displays mitochondrial dysfunction.2013

    • Author(s)
      Minakawa EN, Yamakado H, Tanaka A, Uemura K, Takeda S, Takahashi R
    • Journal Title

      Neurosci Res.

      Volume: 77 Issue: 4 Pages: 228-233

    • DOI

      10.1016/j.neures.2013.09.006

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice2013

    • Author(s)
      Ageta-Ishihara N, Yamakado H, Morita T, Hattori S, Takao K, Miyakawa T, Takahashi R, Kinoshita M
    • Journal Title

      Mol Brain

      Volume: 6 Issue: 1 Pages: 35-35

    • DOI

      10.1186/1756-6606-6-35

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats.2013

    • Author(s)
      Nuber S, et al.
    • Journal Title

      Brain

      Volume: 136 Issue: 2 Pages: 412-432

    • DOI

      10.1093/brain/aws358

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] PINK1 and Parkin complementarily protect dopaminergic neurons in vertebrates.2013

    • Author(s)
      Matsui H, Gavinio R, Asano T, Uemura N, Ito H, Taniguchi Y, Kobayashi Y, Maki T, Shen J, Takeda S, Uemura K, Yamakado H, Takahashi R.
    • Journal Title

      Hum Mol Genet

      Volume: 22(12) Issue: 12 Pages: 2423-2434

    • DOI

      10.1093/hmg/ddt095

    • Related Report
      2012 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] α-Synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior and hyperlocomotion2012

    • Author(s)
      Yamakado H, Moriwaki Y, Yamasaki N, Miyakawa T, Kurisu J, Uemura K, Inoue H, Takahashi M, Takahashi R
    • Journal Title

      Neurosci Res.

      Volume: 73 Pages: 173-7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] α-Synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior and hyperlocomotion.2012

    • Author(s)
      Yamakado H
    • Journal Title

      Neurosci Res

      Volume: 73(2) Issue: 2 Pages: 173-7

    • DOI

      10.1016/j.neures.2012.03.010

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] PINK1と Parkinは脊椎動物において相補的にミトコンドリアを保護する2013

    • Author(s)
      浅野剛史、松井秀彰、Robert Gavinio、上村紀人、伊東秀文、谷口善仁、Jie Shen、武田俊一、植村健吾、山門穂高、髙橋良輔
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Viable Gaucher's disease model of medaka fish completely deficienct in glucocerebrosidase activity developed alpha-synuclein aggregation in the brain2013

    • Author(s)
      Norihito Uemura, Tomoko Fujiwara-Ishikawa, Masato Kinoshita, Masato Koike, Hideaki Matsui, Hodaka Yamakado, Kengo Uemura, Yasuo Uchiyama, Takeshi Todo, Shun-ichi Takeda and Ryosuke Takahashi
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      SanDiego
    • Year and Date
      2013-11-10
    • Related Report
      2013 Final Research Report
  • [Presentation] マウスを用いたゾニサミドの作用機序の解析2013

    • Author(s)
      浅野剛史、山門穂高、高橋良輔
    • Organizer
      第7回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      東京
    • Year and Date
      2013-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] GBAノックアウトメダカは脳にアルファシヌクレイン凝集体を形成する2013

    • Author(s)
      上村紀仁、石川智子、木下政人、小池正人、松井秀彰、山門穂高、植村健吾、内山安男、藤堂剛、武田俊一、高橋良輔
    • Organizer
      日本 Cell death学会
    • Place of Presentation
      京都
    • Year and Date
      2013-07-19
    • Related Report
      2013 Final Research Report
  • [Presentation] PINK1と Parkinは脊椎動物において相補的にミトコンドリアを保護する2013

    • Author(s)
      浅野剛史、松井秀彰、Robert Gavinio、上村紀人、伊東秀文、谷口善仁、JieShen、武田俊一、植村健吾、山門穂高、髙橋良輔
    • Organizer
      第22回日本 CellDeath学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2013-07-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Viable Gaucher's disease model of medaka fish completely deficienct in glucocerebrosidase activity developed alpha-synucleinaggregation in the brain2013

    • Author(s)
      Norihito Uemura, Tomoko Fujiwara-Ishikawa, Masato Kinoshita, Masato Koike, Hideaki Matsui, Hodaka Yamakado, Kengo Uemura, Yasuo Uchiyama, Takeshi Todo, Shun-ichi Takeda and Ryosuke Takahashi
    • Organizer
      日本神経科学学会
    • Place of Presentation
      京都
    • Year and Date
      2013-06-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Viable Gaucher's disease model of medaka fish completely deficienct in glucocerebrosidase activity developed alpha-synuclein aggregation in the brain2013

    • Author(s)
      Norihito Uemura, Tomoko Fujiwara-Ishikawa, Masato Kinoshita, Masato Koike, Hideaki Matsui, Hodaka Yamakado, Kengo Uemura, Yasuo Uchiyama, Takeshi Todo, Shun-ichi Takeda and Ryosuke Takahashi
    • Organizer
      17th international congress of Parkinson's disease and movement disorders
    • Place of Presentation
      Sydney
    • Year and Date
      2013-06-20
    • Related Report
      2013 Final Research Report
  • [Presentation] α-Synucleinの発現量の調節を標的とするパーキンソン病治療薬剤のスクリーニング2013

    • Author(s)
      浅野剛史、山門穂高、高橋良輔
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Year and Date
      2013-06-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Therapeutic approach to Parkinson's disease by modifying α-synuclein expression2013

    • Author(s)
      Yamakado H, Asano T, Takahashi, R
    • Organizer
      TheMDS 17th International Congress of Parkinson's Diseaseand Movement Disorders
    • Place of Presentation
      Sydney
    • Year and Date
      2013-06-17
    • Related Report
      2013 Final Research Report
  • [Presentation] メダカを用いたGBA変異とパーキンソン病の関連性の解析2013

    • Author(s)
      上村紀仁、石川智子、木下政人、小池正人、松井秀彰、山門穂高、植村健吾、内山安男、藤堂剛、武田俊一、高橋良輔
    • Organizer
      日本神経学会
    • Place of Presentation
      東京
    • Year and Date
      2013-05-31
    • Related Report
      2013 Final Research Report
  • [Presentation] 疾患特異的iPS細胞モデルによる遺伝性パーキンソン病の研究2013

    • Author(s)
      小芝泰、森実飛鳥、山門穂高、菊地哲広、土井大輔、西村周泰、皆川栄子江川斉宏、近藤孝之、井上治久、髙橋淳、髙橋良輔
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 疾患特異的iPS細胞モデルによる遺伝性パーキンソン病の研究2013

    • Author(s)
      小芝泰、森実飛鳥、山門穂高、菊地哲広、皆川栄子、土井大輔、西村周泰, 江川斉宏、井上治久、髙橋淳、髙橋良輔
    • Organizer
      第54回日本神経学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 疾患特異的iPS細胞モデルによるLRRK2変異パーキンソン病の研究2013

    • Author(s)
      小芝泰、森実飛鳥、山門穂高、陣上直人、菊地哲広、土井大輔、皆川栄子、江川斉宏、井上治久、髙橋淳、髙橋良輔
    • Organizer
      第7回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] ATP13A2 (PARK9)変異メダカの解析2012

    • Author(s)
      樽野陽亮、松井秀彰、上村紀仁、山門穂高、高橋良輔
    • Organizer
      第6回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      京都
    • Year and Date
      2012-10-13
    • Related Report
      2013 Final Research Report
  • [Presentation] BACテクノロジーを用いたパーキンソン病の治療薬候補の探索2012

    • Author(s)
      浅野剛史、山門穂高、高橋良輔
    • Organizer
      第6回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      京都
    • Year and Date
      2012-10-13
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] メダカを用いたGBA変異とパーキンソン病の関連性の解析2012

    • Author(s)
      上村紀仁、石川‐藤原智子、山門穂高、植村健吾、藤堂剛、高橋良輔
    • Organizer
      第6回パーキンソン病・運動障害疾患コングレス(MDSJ)
    • Place of Presentation
      京都
    • Year and Date
      2012-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] ATP13A2(PARK9)変異メダカの解析2012

    • Author(s)
      樽野陽亮、松井秀彰、斉藤太郎、吉村淳、森下真一、重信秀治、田中実、上村紀仁、山門穂高、高橋良輔
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Compensational relationship betweenParkin and PINK12012

    • Author(s)
      Gavinio, R. Matsui, H. Ito, H. Taniguchi, Y. Yamakado, H. Maki, T.Sawada, T. Takeda, S. Takahashi, R
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-20
    • Related Report
      2013 Final Research Report
  • [Presentation] メダカを用いたGBA変異とパーキンソン病の関連性の解析2012

    • Author(s)
      上村紀仁、石川‐藤原智子、山門穂高、植村健吾、藤堂剛、高橋良輔
    • Organizer
      日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-20
    • Related Report
      2013 Final Research Report
  • [Presentation] α-synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior2012

    • Author(s)
      Yamakado, H. Moriwaki, Y. Yamasaki, N. Miyakawa, T. Kurisu, J. Uemura, K. Inoue, H. Takahashi ,M. Takahashi, R
    • Organizer
      The MDS 17th International Congress of Parkinson's Disease and Movement Disorders
    • Place of Presentation
      Dablin, Ireland
    • Year and Date
      2012-06-21
    • Related Report
      2013 Final Research Report
  • [Presentation] CONGNITIVE AND PHYCHIATRIC FEATURES IN ANIMAL PD MODELS2012

    • Author(s)
      Takahashi, R., Yamakado, H., Gavinio, R
    • Organizer
      8th International Congress On Mental Dysfunction & Other Non-Motor Features In Parkinson's Disease and Related Disorders
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2012-05-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Therapeutic approach to Parkinson's disease by modifying α-synuclein expression.

    • Author(s)
      Yamakado H, Asano T, Takahashi, R.
    • Organizer
      The MDS 17th International Congress of Parkinson's Disease and Movement Disorders
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2013 Annual Research Report
  • [Presentation] α-synuclein BAC transgenic mice as a model for Parkinson’s disease manifested decreased anxiety-like behavior

    • Author(s)
      Yamakado H, Moriwaki Y, N, Miyakawa T, Kurisu J, Uemura K, Inoue H, Takahashi M, Takahashi R
    • Organizer
      The MDS 17th International Congress of Parkinson's Disease and Movement Disorders
    • Place of Presentation
      dablin, Ireland
    • Related Report
      2012 Research-status Report
  • [Presentation] メダカを用いたGBA変異とパーキンソン病の関連性の解析

    • Author(s)
      上村紀仁、石川‐藤原智子、山門穂高、植村健吾、藤堂剛、高橋良輔
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] ATP13A2 (PARK9)変異メダカの解析

    • Author(s)
      樽野 陽亮、松井秀彰、斉藤太郎、吉村淳、森下真一、重信秀治、田中実、上村紀仁、山門穂高、高橋良輔
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] Compensational relationship between Parkin and PINK1

    • Author(s)
      Gavinio R, Matsui H, Ito H, Taniguchi Y, Yamakado H, Maki T, Sawada T,Takeda S, Takahashi R
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] メダカを用いたGBA変異とパーキンソン病の関連性の解析

    • Author(s)
      上村紀仁、石川‐藤原智子、山門穂高、植村健吾、藤堂剛、高橋良輔
    • Organizer
      第6回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] ATP13A2(PARK9)変異メダカの解析

    • Author(s)
      樽野陽亮、松井秀彰、上村紀仁、山門穂高、高橋良輔
    • Organizer
      第6回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Book] 孤発性パーキンソン病、日本臨床別冊神経症候群第2版2014

    • Author(s)
      山門穂高, 他
    • Related Report
      2013 Final Research Report
  • [Book] パーキンソン病と運動異常Movement disorderの病因、アクチュアル脳神経疾患の臨床2013

    • Author(s)
      山門穂高, 他
    • Related Report
      2013 Final Research Report
  • [Book] パーキンソン病の薬物療法、今日の神経疾患治療指針(第2版)2013

    • Author(s)
      山門穂高, 他
    • Related Report
      2013 Final Research Report
  • [Book] 心と体のクロストークから解く精神・神経疾患発症基盤・病態生理を担う分子カスケードから臨床応用まで、実験医学増刊2012

    • Author(s)
      山門穂高, 他
    • Related Report
      2013 Final Research Report
  • [Book] パーキンソン病動物モデル、神経内科2012

    • Author(s)
      山門穂高, 他
    • Related Report
      2013 Final Research Report
  • [Remarks] ホームページ(京都大学神経内科)

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~neurology/index.html

    • Related Report
      2013 Final Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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