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

• Project/Area Number: 24790879
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kyoto 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: ¥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.

Research Products

• [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
  • Peer Reviewed / Open Access
• [Journal Article] Exploring the Pathogenetic Mechanisms underlying Parkinson's Disease in Medaka Fish (2013)
  • Author(s): Matsui H, Uemura N, Yamakado H, Takeda S, Takahashi R
  • Journal Title: J Parkinsons Dis.
  • Peer Reviewed
• [Journal Article] The function of parkin : revisited (2013)
  • Author(s): Yamakado H, Takahashi R
  • Journal Title: Mov Disord. Volume: 14 Pages: 1936-1936
  • 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
  • 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.
  • Peer Reviewed
• [Journal Article] Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice (2013)
  • 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
  • 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 Pages: 2423-34
  • Peer Reviewed
• [Journal Article] A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats (2013)
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson's disease, causes behavioral alterations but not neurodegeneration in mice (2013)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access
• [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, 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
  • 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
  • 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
• [Presentation] Viable Gaucher's disease model of medaka fish completely deficienct in glucocerebrosidase activity developed alpha-synuclein aggregation in the brain (2013)
  • 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
• [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
• [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
• [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
• [Presentation] Viable Gaucher's disease model of medaka fish completely deficienct in glucocerebrosidase activity developed alpha-synucleinaggregation in the brain (2013)
  • 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
• [Presentation] Viable Gaucher's disease model of medaka fish completely deficienct in glucocerebrosidase activity developed alpha-synuclein aggregation in the brain (2013)
  • 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
• [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
• [Presentation] Therapeutic approach to Parkinson's disease by modifying α-synuclein expression (2013)
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Compensational relationship betweenParkin and PINK1 (2012)
  • 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
• [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
• [Presentation] α-synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior (2012)
  • 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
• [Presentation] CONGNITIVE AND PHYCHIATRIC FEATURES IN ANIMAL PD MODELS (2012)
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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