Molecular mechanisms of cell death in synucleinopathy

• Project/Area Number: 19590978
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: TAKEDA Atsushi Tohoku University, 大学院・医学系研究科, 准教授 (70261534)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: シヌクレイノパチー / パーキンソン病 / 多系統萎縮症 / 神経細胞死 / 神経変性 / シヌクレノパチー / αシヌクレン / アポトーシス / 小胞体ストレス / ミトコンドリア / αシヌクレイン

Research Abstract

In wild-type α-synuclein cells treated with rotenone, induction of unfolded protein response (UPR) markers were evident several hours before the induction of mitochondrial disruption and caspase-3 activation. On the other hand, the S129A mutant failed to activate UPRs. It seems plausible that α-synuclein toxicity is dependent on the phosphorylation at S129 that induces the UPRs.

Research Products

• [Journal Article] Functional imaging studies of hyposmia in Parkinson's disease (2010)
  • Author(s): Takeda A., Saito N., Baba T., Kikuchi A., Sugeno N., Kobayashi M., Hasegawa T., Itoyama Y.
  • Journal Title: J.Neurol.Sci. 289 Pages: 36-39
  • Peer Reviewed
• [Journal Article] In vivo visualization of α-synuclein deposition by carbon-11-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro] ethoxy)benzoxazole positron emission tomography in multiple system atrophy (2010)
  • Author(s): Kikuchi A., Takeda A., Okamura N., Tashiro M., Hasegawa T., Furumoto S., Kobayashi M., Sugeno N., Baba T., Miki Y., Mori F., Wakabayashi K., Funaki Y., Iwata R., Takahashi S., Fukuda H., Arai H., Kudo Y., Yanai K, Itoyama Y.
  • Journal Title: Brain (in press)
  • Peer Reviewed
• [Journal Article] CSF protein biomarkers for proximal axonal damage improve prognostic accuracy in the acute phase of Guillain-Barre Syndrome (2009)
  • Author(s): Petzold A., Brettschneider J., Jin K., Keir G., Murray N.M.F., Hirsch N.P., Itoyama Y., Reilly M.M., Takeda A., Tumani H.
  • Journal Title: Muscle Nerve 40 Pages: 42-49
  • Peer Reviewed
• [Journal Article] Narcolepsy as an initial manifestation of neuromyelitis optica with antiaquaporin-4 antibody (2009)
  • Author(s): Baba T., Nakashima I., Kanbayashi T., Konno M., Takahashi T., Fujihara K., Misu T., Takeda A., Shiga Y., Ogawa H., Itoyama Y.
  • Journal Title: J.Neurol. 256 Pages: 287-8
  • Peer Reviewed
• [Journal Article] Do parkinsonian patients have trouble telling lies? : The neurobiological basis of deceptive behavior (2009)
  • Author(s): Abe N., Fujii T., Hirayama K., Takeda A., Hosokai Y., Ishioka T., Nishio Y., Suzuki K., Itoyama Y., Takahashi S., Fukuda H., Mori E.
  • Journal Title: Brain 132 Pages: 1386-1395
  • Peer Reviewed
• [Journal Article] Distinct patterns of regional cerebral glucose metabolism in Parkinson's disease with and without mild cognitive impairment (2009)
  • Author(s): Hosokai Y., Nishio Y., Hirayama K., Takeda A., Ishioka T., Sawada Y., Suzuki K., Itoyama Y., Takahashi S., Fukuda H., Mori E.
  • Journal Title: Mov.Disord. 24 Pages: 854-862
  • Peer Reviewed
• [Journal Article] Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease (2009)
  • Author(s): Su B., Liu H., Wang X., Chen SG., Siedlak SL., Kondo E., Choi R., Takeda A., Castellani RJ., Perry G., Smith MA., Zhu X., Lee HG.
  • Journal Title: Mol.Neurodeg. 4 Pages: 32-32
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease (2009)
  • Author(s): Satake W., Nakabayashi Y., Mizuta I., Hirota Y., Ito C., Kubo M., Kawaguchi T., Tsunoda T., Watanabe M., Takeda A., Tomiyama H., Nakashima K., Hasegawa K., Obata F., Yoshikawa T., Kawakami H., Sakoda S., Yamamoto M., Hattori N., Murata M., Nakamura Y., Toda T.
  • Journal Title: Nature Genet. 41 Pages: 1303-1307
  • Peer Reviewed
• [Journal Article] Do parkinsonian patients have trouble telling lies? : The neurobiologic al basis of deceptive behavior. (2009)
  • Author(s): Abe N., et al.
  • Journal Title: Brain 132 Pages: 1386-1395
  • Peer Reviewed
• [Journal Article] Distinct patterns of regional cerebral glucose metabolism in Parkinson's disease with and without mild cognitive impairment. (2009)
  • Author(s): Hosokai Y., et al.
  • Journal Title: Mov.Disord. 24 Pages: 854-862
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. (2009)
  • Author(s): Satake W., et al
  • Journal Title: Nature Genet. 41 Pages: 1303-1307
  • Peer Reviewed
• [Journal Article] Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease. (2009)
  • Author(s): Su B., et al.
  • Journal Title: Mol.Neurodeg. 4:32 Pages: 1-5
  • Peer Reviewed
• [Journal Article] PARK9-linked parkinsonism in Eastern Asia : Mutation detection in ATP13A2 and clinical phenotype (2008)
  • Author(s): Ning YP, 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
  • Peer Reviewed
• [Journal Article] Ser129 phosphorylation of α-synuclein induces unfolded protein response mediated cell death (2008)
  • Author(s): Sugeno N., Takeda A., Hasegawa T., Kobayashi M., Kikuchi A., Mori F., Wakabayashi K., Itoyama Y.
  • Journal Title: J.Biol Chem. 283: Pages: 23179-23188
  • Peer Reviewed
• [Journal Article] Nucleic acid oxidation in Alzheimer disease (2008)
  • Author(s): Moreira PI., Nunomura A., Nakamura M., Takeda A., Shenk JC., Aliev G., Smith MA., Perry G.
  • Journal Title: Free Radic Biol Med. 44 Pages: 1493-505
  • Peer Reviewed
• [Journal Article] Sublethal RNA oxidation as a mechanism for neurodegenerative disease (2008)
  • Author(s): Castellani RJ., Nunomura A., Rolston RK., Moreira PI., Takeda A., Perry G., Smith MA.
  • Journal Title: Int.J.Mol.Sci. 9 Pages: 789-806
  • Peer Reviewed
• [Journal Article] PARK9-linked parkinsonism in Eastern Asia : Mutation detection in ATP13A2 and clinical phenotype (2008)
  • Author(s): Ning YP, Kanai K., et.al.
  • Journal Title: Neurology 70 Pages: 1491-1493
  • Peer Reviewed
• [Journal Article] Ser129 phosphorylation of α-synuclein induces unfolded protein response mediated cell death (2008)
  • Author(s): Sugeno N., Takeda A., et.al.
  • Journal Title: J. Biel Chem 238 Pages: 23179-23188
  • Peer Reviewed
• [Journal Article] Nucleic acid oxidation in Alzheimer disease (2008)
  • Author(s): Moreira PI., Nunomura A., et.al.
  • Journal Title: Free Radic Biol Med 44 Pages: 1493-1505
  • Peer Reviewed
• [Journal Article] Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites. (2007)
  • Author(s): Hasegawa T., Sugeno N., Takeda A., Matsuzaki-Kobayashi M., Kikuchi A., Furukawa K., Miyagi T., Itoyama Y.
  • Journal Title: FEBS Lett. 581 Pages: 406-412
  • Peer Reviewed
• [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, MurataM, Toda T.,
  • Journal Title: Neuroreport 18 Pages: 937-940
  • Peer Reviewed
• [Journal Article] Olfactory dysfunction in Parkinson's disease. (2007)
  • Author(s): Takeda A., Kikuchi A., Itoyama Y.
  • Journal Title: J. Neurol. 254(sup.4) Pages: 2-7
• [Presentation] 嗅覚異常、シンポジウム「パーキンソン病の診断をめぐる新機軸」 (2009)
  • Author(s): 武田篤
  • Organizer: 第62回日本自律神経学会
  • Place of Presentation: 和歌山
  • Year and Date: 2009-11-06
• [Presentation] Dopamine Dysregulation Syndrome、シンポジウム「PD・DLBの認知・行動障害」 (2009)
  • Author(s): 武田篤
  • Organizer: 第14回日本精神神経医学会
  • Place of Presentation: 仙台
  • Year and Date: 2009-11-05
• [Presentation] パーキンソン病の病態:運動症候と非運動症候 (2009)
  • Author(s): 武田篤, 他
  • Organizer: 第51回 日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-22
• [Presentation] パーキンソン病の病態 : 運動症候と非運動症候、シンポジウム「パーキンソン病の病因・診断・治療研究の進歩」 (2009)
  • Author(s): 武田篤
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] 痙性斜頚患者における脳代謝の検討 (2009)
  • Author(s): 菊池昭夫, 武田篤, 馬場徹, 菅野直人, 小林理子, 長谷川隆文, 田代学, 四月朔日聖一, 伊藤正敏, 関和則, 糸山泰人
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] パーキンソン病におけるαSYN自己抗体の存在およびオリゴマークリアランスへの関与 (2009)
  • Author(s): 長谷川隆文, 武田篤, 菊池昭夫, 菅野直人, 小林理子, 馬場徹, 糸山泰人
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] チロシン水酸化酵素発現細胞における細胞死 (2009)
  • Author(s): 菅野直人, 小林理子, 武田篤, 長谷川隆文, 菊池昭夫, 馬場徹, 糸山泰人
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] GCI形成過程における Tubulin polymerization promoting protein の機能的役割 (2009)
  • Author(s): 小林理子, 長谷川隆文, 武田篤, 菅野直人, 菊池昭夫, 馬場徹, 糸山泰人
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] パーキンソン病患者における嗅覚障害の神経基盤の検討 (2009)
  • Author(s): 馬場徹, 菅野直人, 小林理子, 菊池昭夫, 長谷川隆文, 武田篤, 糸山泰人, 平山一美, 森悦朗
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] レビー小体がなければパーキンソン病とはいえない・Yes (2009)
  • Author(s): 武田篤
  • Organizer: 第3回MDSJ
  • Place of Presentation: 東京
• [Presentation] Changes in brain metabolism and dysphagia in Parkinson's disease (2009)
  • Author(s): Kikuchi A., Takeda A., Baba, T. Sugeno N., Kobayashi M., Hasegawa T., Mori E., Itoyama Y.
  • Organizer: 13th International congress of Parkinson's disease and movement disorders
  • Place of Presentation: Paris, France
• [Presentation] Cytoprotective effects of extracellular dopamine under the dopamine overproduction (2009)
  • Author(s): Sugeno N., Kobayashi M., Hasegawa T., Takeda A., Kikuchi A., Baba T., Itoyama Y.
  • Organizer: 13th International congress of Parkinson's disease and movement disorders
  • Place of Presentation: Paris, France
• [Presentation] Changes in brain metabolism and hyposmia in Parkinson's disease (2009)
  • Author(s): Baba T., Takeda A., Kikuchi A., Sugeno N., Kobayashi M., Hasegawa T., Hirayama K., Mori E., Itoyama Y.
  • Organizer: 13th International congress of Parkinson's disease and movement disorders
  • Place of Presentation: Paris, France
• [Presentation] Ser129 phosphorylation of α-synuclein induces unfolded protein response mediated cell death (2008)
  • Author(s): Sugeno N., Takeda A., et.al.
  • Organizer: 12^<th> International congress of Parkinson's disease and movement disorders
  • Place of Presentation: Chicago, USA
  • Year and Date: 2008-06-25
• [Presentation] パーキンソン病の錯綜図認知障害と脳代謝 (2008)
  • Author(s): 平山和美, 石岡俊之, 武田篤, 細貝良行, 鈴木匡子, 西尾憲之, 糸山泰人, 福田寛, 森悦朗
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] パーキンソン病患者における嗅覚低下と脳代謝の検討 (2008)
  • Author(s): 武田篤, 菊池昭夫, 菅野直人, 小林理子, 平山和美, 森悦朗, 糸山泰人
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] 軽度認知障害を有するパーキンソン病患者における大脳局所灰白質量減少 (2008)
  • Author(s): 西尾憲之, 武田篤, 平山和美, 鈴木匡子, 細貝良行, 石岡俊之, 糸山泰人, 森悦朗
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] パーキンソン病感受性遺伝子の同定-FGF20と新規感受性遺伝子- (2008)
  • Author(s): 佐竹渉, 水田依久子, 渡邉雅彦, 武田篤, 長谷川一子, 中島健二, 佐古田三郎, 山本光利, 服部信孝, 村田美穂, 戸田達史
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] パーキンソン病感受性遺伝子の同定および統計学的相互作用解析 (2008)
  • Author(s): 水田依久子, 佐竹渉, 角田達彦, 渡邉雅彦, 武田篤, 長谷川一子, 中島健二, 山本光利, 服部信孝, 村田美穂, 戸田達史
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] ドパミン過剰産生細胞を用いた細胞死メカニズムの検討 : 酸化的ストレスとの関連 (2008)
  • Author(s): 小林理子, 菅野直人, 武田篤, 菊池昭夫, 糸山泰人
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] αシヌクレインリン酸化によって誘導される細胞死は小胞体ストレスを介する (2008)
  • Author(s): 菅野直人, 武田篤, 小林理子, 菊池昭夫, 長谷川隆文, 糸山泰人
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] パーキンソン病患者における嚥下障害と脳代謝の検討 (2008)
  • Author(s): 菊池昭夫, 武田篤, 菅野直人, 小林理子, 長谷川隆文, 細貝良行, 石岡俊之, 西尾憲之, 岡田和枝, 平山和美, 鈴木匡子, 森悦朗, 金田朋洋, 高橋昭喜, 福田寛, 糸山泰人
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] パーキンソン病の病態 : 分子生物学から分かったこと. シンポジウム「パーキンソン病の臨床、基礎の最前線」 (2008)
  • Author(s): 武田篤
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] Wearing-off の機序とその評価、イブニングセミナー「PD治療におけるL-dopa療法を再考する」 (2008)
  • Author(s): 武田篤
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] Lewy 小体は善玉である・YES (2008)
  • Author(s): 武田篤
  • Organizer: 第2回MDSJ
  • Place of Presentation: 京都
• [Presentation] Hyposomnia in Parkinson's disease is associated with changes in cortical metabolism (2008)
  • Author(s): Takeda A., Kikuchi A., Sugeno N., Kobayashi M., Hirayama K., Mori E., Itoyama Y.
  • Organizer: 12th International congress of Parkinson's disease and movement disorders
  • Place of Presentation: Chicago, USA
• [Presentation] Ser129 phosphorylation of α-synuclein induces unfolded protein response mediated cell death (2008)
  • Author(s): Sugeno N., Takeda A., Hasegawa T., Kobayashi M., Kikuchi A., Itoyama Y.
  • Organizer: 12th International congress of Parkinson's disease and movement disorders
  • Place of Presentation: Chicago, USA
• [Presentation] PET and fMRI of Olfaction in PD (2008)
  • Author(s): Takeda A.
  • Organizer: 6th International Congress on mental dysfunctions & other non-motor features in Parkinson's disease
  • Place of Presentation: Dresden, Germany