Identification of a common pathway among gene products for familial Parkinson's disease and screening for a novel causative gene for

• Project/Area Number: 19390244
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: HATTORI Nobutaka Juntendo University, 医学部, 教授 (80218510)
• Co-Investigator(Kenkyū-buntansha): KUBO Shinitiro 順天堂大学, 医学部, 准教授 (20327795) ; SATO Shigeto 順天堂大学, 医学部, 准教授 (00445537) ; TOMIYAMA Hiroyuki 順天堂大学, 医学部, 助教 (20515069) ; 平澤 基之 順天堂大学, 医学部, 准教授 (90338393) ; 佐藤 健一 順天堂大学, 医学部, 准教授 (00276461)
• Co-Investigator(Renkei-kenkyūsha): IWAI Kazyhiro 大阪大学, 医学研究科, 教授 (60252459)
• Research Collaborator: SAKATA Shinithi 大阪大学, 医学研究科
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2008: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: パーキンソン病 / 遺伝性パーキンソン病 / 共通機構 / 新規原因遺伝子 / 劣性遺伝性パーキンソン病 / ミトコンドリア機能 / PINK1 / Parkin / DJ-1 / autophagy-lysosomal path& / ATP132 / ユビキチン化 / 常染色体劣性晩発性パーキンソン病 / 連鎖解析

Research Abstract

遺伝性パーキンソン病(FPD)の病態には共通してドパミン反応性パーキンソニズムがある。従って共通した機構が存在していることが予想される。現在、孤発型PDと鑑別が依然これら遺伝子産物の詳細な機能は不明である。本課題ではparkinとPINK1の相互作用を検討し、両分子はミトコンドリア外膜で会合し、parkinはPINK1の安定性に関与していることが分かった。またFPDにおいては半数以上が、原因遺伝子が不明であり、新規原因遺伝子座を決定した。

Research Products

• [Journal Article] Visual impairment in Parkinson's disease treated with amantadine : case report and review of the literature (2008)
  • Author(s): Kubo S, Iwatake A, Ebihara N, Murakami A, Hattori N
  • Journal Title: Parkinsonism Relat Disord 14(2) Pages: 166-9
• [Journal Article] Familial parkinsonism with digenic parkin and PINK1 mutations (2008)
  • Author(s): Funayama M, Li Y, Tsoi TH, Lam CW, Ohi T, Yazawa S, Uyama E, Djaldetti R, Melamed E, Yoshino H, Imamichi Y, Takashima H, Nishioka K, Sato K, Tomiyama H, Kubo S, MD, Mizuno Y, Hattori N
  • Journal Title: Mov Disord 65 Pages: 802-808
• [Journal Article] Mutation analysis of the PINK1 gene in 391 patients with Parkinson disease (2008)
  • Author(s): Kumazawa R, Tomiyama H, Li Y, Imamichi Y, Funayama M, Yoshino H, Yokochi F, Fukusako T, Takehisa Y, Kashihara K, Kondo T, Elibol B, Bostantjopoulou S, Toda T, Takahashi H, Yoshii F, Mizuno Y, Hattori N
  • Journal Title: Arch Neurol 65(6) Pages: 802-8
• [Journal Article] PARK9-linked parkinsonism in Eastern Asia : Mutation detection in ATP13A2 andclinical phenotype (2008)
  • Author(s): Ning Y, Kanai K, Tomiyama H, Li Y, Funayama M, Yoshino H, Sato S, Asahina M, Kuwabara S, Takeda A, Hattori T, Mizuno Y, Hattori N
  • Journal Title: Neurology 70 Pages: 1491-1493
• [Journal Article] Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease (2008)
  • Author(s): Ross OA, Wu YR, Lee MC, Funayama M, Chen ML, Soto AI, Mata IF, Lee-Chen GJ, Chen CM, Tang M, Zhao Y, Hattori N, Farrer MJ, Tan EK, Wu RM
  • Journal Title: Ann Neurol 64 Pages: 88-92
• [Journal Article] Mutation analyses in amyotrophic lateral sclerosis/parkinsonism-dementia complex of Kii, Japan (2008)
  • Author(s): Tomiyama H, Kokubo Y, Sasaki R, Li Y, Imamichi Y, Funayama M, Mizuno Y, Hattori N, Kuzuhara S
  • Journal Title: Mov Disord 23 Pages: 2344-2348
• [Journal Article] LRRK2 P755L variant in sporadic Parkinson's disease (2008)
  • Author(s): Tomiyama H, Mizuta I, Li Y, Funayama M, Yoshino H, Li L, Murata M, Yamamoto M, Kubo S, Mizuno Y, Toda T, Hattori N
  • Journal Title: J Hum Genet 53 Pages: 1012-5
  • NAID: 10025584966
• [Journal Article] PARK2 mutations and clinical features in a Chinese population with early-onset Parkinson's disease (2008)
  • Author(s): Chan DK, Mok V, Ng PW, Yeung J, Kwok JB, Fang ZM, Clarke R, Wong L, Schofield PR, Hattori N
  • Journal Title: J Neural Transm 115 Pages: 715-9
• [Journal Article] Animal models of Parkinson's disease : similarities and differences between the disease andmodels (2008)
  • Author(s): Hattori N, Sato S
  • Journal Title: Neuropathology 27 Pages: 479-83
• [Journal Article] Wireless voltammetry recording in unanesthetised behaving rats (2008)
  • Author(s): Kagohashi M, Nakazato T, Yoshimi K, Moizumi S, Hattori N, Kitazawa S
  • Journal Title: Neurosci Res 60 Pages: 120-7
• [Journal Article] Progress in the pathogenesis and genetics of Parkinson's disease (2008)
  • Author(s): Mizuno Y, Hattori N, Kubo SI, Sato S, Nishioka K, Hatano T, Tomiyama H, Funayama M, Machida Y, Mochizuki H. Review
  • Journal Title: Philos Trans R Soc Lond B Biol Sci 27 Pages: 2215-2227
• [Journal Article] Mutation analysis of the PINK1 gene in 391 patients with Parkinson disease. 2008 Jun ; 65(6) : 802-8 (2008)
  • Author(s): Kumazawa R, et al.
  • Journal Title: Arch Neurol 65 Pages: 802-808
  • Peer Reviewed
• [Journal Article] Familial parkinsonism with digenic parkin and PINK1 mutations (2008)
  • Author(s): Funayama M, et al.
  • Journal Title: Mov Disord 65 Pages: 802-808
  • Peer Reviewed
• [Journal Article] PARK9-linked parkinsonism in Eastern Asia : Mutation detection in ATP13A2 and clinical phenotype (2008)
  • Author(s): Ning YP, et al.
  • Journal Title: Neurology 70 Pages: 1491-1493
  • Peer Reviewed
• [Journal Article] Leucine-rich repeat kinase 2 associates with lipid rafts (2007)
  • Author(s): Hatano T, Hattori N, et al.
  • Journal Title: Human Mol Genet 16 Pages: 678-690
• [Journal Article] Sept4, a component of presynaptic Scaffold and Lewy bodies, is required for the suppression of alpha-synuclein neurotoxicity (2007)
  • Author(s): Ihara M, , Hattori N, et al.
  • Journal Title: Neuron 53 Pages: 519-533
• [Journal Article] LRRK2 G2385R variant is a risk factor for Parkinson disease in Asian population (2007)
  • Author(s): Funayama M, Hattori N, et al.
  • Journal Title: NeuroReport 18 Pages: 273-275
• [Journal Article] Fabrication, characterization, and application of boron-doped diamond microelectrodes for in vivo dopamine detection (2007)
  • Author(s): Suzuki A, Ivandini TA, Yoshimi K, Fujishima A, Oyama G, Nakazato T, Hattori N, Kitazawa S, Einaga Y
  • Journal Title: Anal Chem 79 Pages: 8608-15
• [Journal Article] Correlation between levels of pigment epithelium-derived factor and vascular endothelial growth factor in the striatum of patients with Parkinson's disease (2007)
  • Author(s): Yasuda T, Fukuda-Tani M, Nihira T, Wada K, Hattori N, Mizuno Y, Mochizuki H
  • Journal Title: Exp Neurol 206 Pages: 308-17
• [Journal Article] Fibroblast growth factor 20 gene and Parkinson's disease in the Japanese population (2007)
  • Author(s): Satake W, Mizuta I, Suzuki S, Nakabayashi Y, Ito C, Watanabe M, Takeda A, Hasegawa K, Sakoda S, Yamamoto M, Hattori N, Murata M, Toda T
  • Journal Title: Neuroreport 18 Pages: 937-40
• [Journal Article] Parkin is expressed in vascular endothelial cells (2007)
  • Author(s): Tamo W, Imaizumi T, Tanji K, Yoshida H, Takanashi S, Wakabayashi K, Takahashi R, Hattori N, Satoh K
  • Journal Title: Neurosci Lett 419 Pages: 199-201
• [Journal Article] Leucine-rich repeat kinase 2 associates with lipid rafts (2007)
  • Author(s): Hatano T, Kubo S, Imai S, Maeda M, Ishikawa K, Mizuno Y, Hattori N
  • Journal Title: Hum Mol Genet 16 Pages: 678-90
• [Journal Article] Leucine-rich repeat kinase 2 G2385R variant is a risk factor for Parkinson disease in Asian population (2007)
  • Author(s): Funayama M, Li Y, Tomiyama H, Yoshino H, Imamichi Y, Yamamoto M, Murata M, Toda T, Mizuno Y, Hattori N
  • Journal Title: Neuroreport 18 Pages: 273-5
• [Journal Article] Mitochondrial dysfunction in Parkinson's disease (2007)
  • Author(s): Fukae J, Mizuno Y, Hattori N
  • Journal Title: Mitochondrion 7 Pages: 58-62
  • NAID: 40021018096
• [Journal Article] Sept4. a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity (2007)
  • Author(s): Ihara M, Yamasaki N, Hagiwara A, Tanigaki A, Kitano A, Hikawa R, Tomimoto H, Noda M, Takanashi M, Mori H, Hattori N, Miyakawa T, Kinoshita M
  • Journal Title: Neuron 53 Pages: 519-33
• [Journal Article] Neuropsychiatric and cognitive features in autosomal-recessive early parkinsonism due to PINK1 mutations (2007)
  • Author(s): Ephraty L, Porat O, Israeli D, Cohen OS, Tunkel O, Yael S, Hatano Y, Hattori N, Hassin-Baer S
  • Journal Title: Mov Disord 22 Pages: 566-9
• [Journal Article] Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier (2007)
  • Author(s): Kono S, Shirakawa K, Ouchi Y, Sakamoto M, Ida H, Sugiura T, Tomiyama H, Suzuki H, Takahashi Y, Miyajima H, Hattori N, Mizuno Y
  • Journal Title: J Neurol Sci 252 Pages: 181-4
• [Journal Article] Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families (2007)
  • Author(s): Ishihara L, Gibson RA, Warren L, Amouri R, Lyons K, Wielinski C, Hunter C, Swartz JE, Elango R, Akkari PA, Leppert D, Surh L, Reeves KH, Thomas S, Ragone L, Hattori N, Pahwa R, Jankovic J, Nance M, Freeman A, Gouider-Khouja N, Kefi M, Zouari M, Ben Sassi S, Ben Yahmed S, ElEuch-Fayeche G, Middleton L, Burn DJ, Watts RL, Hentati F
  • Journal Title: Mov Disord 22 Pages: 55-61
• [Journal Article] Leucine-rich repeat kinase 2 associates with lipid rafts (2007)
  • Author(s): Hatano T., Hattori N., et. al.
  • Journal Title: Human Mol Genet 16 Pages: 678-690
  • Peer Reviewed
• [Journal Article] Sept4,a component of presynaptic Scaffold and Lewy bodies,is required for the suppression of alpha-synuclein neurotoxicity (2007)
  • Author(s): Ihara M., Hattori N., et. al.
  • Journal Title: Neuron 53 Pages: 519-533
  • Peer Reviewed
• [Journal Article] LRRK2 G2385R variant is a risk factor for Parkinson disease in Asianpopulation (2007)
  • Author(s): Funayama M., Hattori N., et. al.
  • Journal Title: NeuroReport 18 Pages: 273-275
  • Peer Reviewed
• [Presentation] NDUFV2+/-マウスにおけるMPTP感受性の検討 (2008)
  • Author(s): 舩山学, 大橋聡, 市川直樹, 今井哲司, 山本庄司, 日下弘道, 板谷昌子, 平澤恵理, 水野美邦, 服部信孝
  • Organizer: 第8回日本ミトコンドリア学会年会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-20
• [Presentation] Autosomal recessive late onset parkinsonismの原因遺伝子探索 (2008)
  • Author(s): 舩山学, 吉野浩代, 今道洋子, 李元哲, 李林, 増田浩美, 板谷昌子, 高梨雅史, 高嶋博, 松浦英治, 有村公良, 野元三治, 富山弘幸, 久保紳一郎, 水野美邦, 服部信孝
  • Organizer: 第2回Movement Disorder Society, Japan学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-04
• [Presentation] NDUFV2+/-マウスにおけるMPTP感受性の検討 (2008)
  • Author(s): 舩山学, 大橋聡, 市川直樹, 今井哲司, 山本庄司, 日下弘道, 板谷昌子, 平澤恵理, 水野美邦, 服部信孝
  • Organizer: 生体機能と創薬シンポジウム2008東京
  • Place of Presentation: 東京
  • Year and Date: 2008-09-05
• [Presentation] Parkinson's disease in Asia (2008)
  • Author(s): Hattori N
  • Organizer: GEPOD meeting
  • Place of Presentation: Norway
  • Year and Date: 2008-06-09
• [Presentation] Autosomal recessive late onset parkinsonismの原因遺伝子探索 (2008)
  • Author(s): 舩山学, 吉野浩代, 今道洋子, 李元哲, 李林, 増田浩美, 板谷昌子, 高梨雅史, 高嶋博, 松浦英治, 有村公良, 野元三治, 水野美邦, 服部信孝
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] Molecular Genetics & Biology in Parkinson's Disease : Concepts, Approach & Methodology (2007)
  • Author(s): Hattori N
  • Organizer: 1st Asian and Oceania Parkinson's Disease and Movement Disorders Congress
  • Place of Presentation: Singapore
  • Year and Date: 2007-10-22
• [Presentation] Molecular Genetics&Biology in Parkinson's Disease Concepts,Approach&Methodology (2007)
  • Author(s): Hattori N
  • Organizer: 1st Asian and Oceania Parkinson's Diseaseand Movement Disorders Congress
  • Place of Presentation: Singapore
  • Year and Date: 2007-10-22
• [Book] パーキンソン病患者さんに発生する合併症の諸問題と具体的対応策 (2008)
  • Author(s): 名取司保子・服部信孝
  • Publisher: 難病と在宅ケア
• [Book] 薬学セレクト疾患と薬物治療知っておきたいcommon diseases101(富野康日己・望月正隆編) (2008)
  • Author(s): 服部信孝
  • Publisher: 医歯薬出版
• [Book] 高齢者パーキンソン病の治療戦略(座談会) (2008)
  • Author(s): 服部信孝
  • Publisher: Pharma Medica
• [Book] ここまでわかったパーキンソン病研究 (2008)
  • Author(s): 服部 信孝
  • Total Pages: 466
  • Publisher: 医師薬出版
• [Book] 基本治療薬115使い方と禁忌三環系抗うつ薬<服部信孝>塩酸アミトリプチリン トリプタノール(Tryptanol), 67脳血栓症急性期およびクモ膜下出血治療薬<服部信孝>オザグレルナトリウム カタクロット(Cataclot)(富野康日己編) (2007)
  • Author(s): 服部信孝
• [Book] 基本治療薬115使い方と禁忌 富野 康日己 編 三環系抗うつ薬<服部信孝>塩酸アミトリプチリン トリプタノール(Trypanol), 67脳血栓症急性期およびクモ膜下出血治療薬<服部信孝>オザグレルナトリウム カタクロット(Cataclot), キサンボン(Xanbon) (2007)
  • Author(s): 服部 信孝
  • Total Pages: 451
  • Publisher: 中外医学者
• [Remarks] Hattori N, Symposium in the genetics of Parkinson's disease, The annual meeting of Taiwan Neurology Association (Tao-yuan), Taiwan,2007.4.7
• [Remarks] Hattori N, Clinical Features and Molecular mechanisms of Nigral Neuronal Death in Parkinsonism with parfkin Gene Mutation (PARK2), department of Neurology National Taiwan University Hospital College of Medicine National Taiwan University, Taiwan, 2007.4.7
• [Remarks] Hattori N, The Aspects of Motor and non-Motor control with Dopamine Agonists, The opening meeting of PD Center of National Taiwan University Hospital (Taipei), Taiwan, 2007.4.8
• [Remarks] Hattori N, The Aspects of Motor and non-Motor control with Dopamine Agonists, Lecture meeting in Taichung, Taiwan, 2007.4.9
• [Remarks] Hattori N, The Formats of Motor and Non-Motor control with Dopamine agonists, Lecture meeting in Kaohsiung, Taiwan, 2007.4.10
• [Remarks] Hattori N, Pathogenesis of PD : insight obtained from inherited PD, ADPD Korea Japan Joint Meeting, Korea, 2007.4.14
• [Remarks] Hattori N, Protein Degradation System in Parkinson 's disease, the 19th Annual Meeting of KSMCB, Korea, 2007.10.19
• [Remarks] Hattori N, The role of ubiquitin-proteasome system in Parkinson's Disease Duration of Lecture, 1st Asian and Oceania Parkinson's Disease and Movement Disorders Congress, Singapore, 2007.10.21
• [Remarks] Hattori N, Molecular Genetics & Biology in Parkinson's Disease : Concepts, Approach & Methodology, 1st Asian and Oceania Parkinson's Disease and Movement Disorders Congress, Singapore, 2007.10.22
• [Patent(Industrial Property Rights)]