2008 Fiscal Year Final Research Report
Molecular mechanisms of conformational changes of proteins and neurodegeneration in neurodegenerative diseases.
Project/Area Number |
18300117
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | Tokyo Metropolitan Organization for Medical Research |
Principal Investigator |
HASEGAWA Masato Tokyo Metropolitan Organization for Medical Research, 東京都精神医学総合研究所, 副参事研究員 (10251232)
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Project Period (FY) |
2006 – 2008
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Keywords | タウ / αシヌクレイン / TDP-43 / アルツハイマー / パーキンソン |
Research Abstract |
神経変性の共通の分子メカニズムを明らかにすることを目的として、患者脳に蓄積する蛋白質の解析、リコンビナント蛋白質を用いた解析を行った。その結果、同じ4リピートタウが蓄積するPSPとCBDにおいて、蓄積するタウの線維構造が異なっている可能性が示唆された。また、FTLD、ALSに蓄積するユビキチン陽性封入体の構成タンパク質としてリン酸化TDP-43を同定した。さらにαシヌクレインの部位特異抗体を用いて、αシヌクレインのモノマーから線維化への構造変化をとらえることに成功した。
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[Journal Article] TDP-43 in ubiquitinated inclusions in the inferior olives in frontotemporal lobar degeneration and in other neurodegenerative diseases: a degenerative process distinct from normal ageing.2009
Author(s)
Davidson Y, Amin H, Kelley T, Shi J, Tian J, Kumaran R, Lashley T, Lees AJ, Duplessis D, Neary D, Snowden J, Akiyama H, Arai T, Hasegawa M, et al.
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Journal Title
Acta Neuropathol. [Epub ahead of print]
Pages: 0
Peer Reviewed
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[Journal Article] Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS.2008
Author(s)
Inukai Y, Nonaka T, Arai T, Yoshida M, Hashizume Y, Beach TG, Buratti E, Baralle FE, Akiyama H, Hisanaga SI, Hasegawa M,
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Journal Title
FEBS Lett 582
Pages: 2289-2904
Peer Reviewed
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[Journal Article] Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.2008
Author(s)
Hasegawa M, Arai T, Nonaka T, Kametani F, Yoshida M, Hashizume Y, Beach TG, Buratti E, Baralle F, Morita M, Nakano I, Oda T, Tsuchiya K, Akiyama H
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Journal Title
Ann Neurol 64
Pages: 60-70
Peer Reviewed
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[Journal Article] Ultra-high field NMR studies of antibody binding and site-specific phosphorylation of alpha-synuclein.2007
Author(s)
Sasakawa H, Sakata E, Yamaguchi Y, Masuda M, Mori T, Kurimoto E, Iguchi T, Hisanaga SI, Iwatsubo T, Hasegawa M, Kato K
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Journal Title
Biochem Biophys Res Commun 363
Pages: 795-799
Peer Reviewed
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[Journal Article] TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.2006
Author(s)
Arai T*, Hasegawa M*, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T
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Journal Title
Biochem Biophys Res Commun 351
Pages: 602-611
Peer Reviewed
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[Journal Article] Corticobasal degeneration with focal, massive tau accumulation in the subcortical white matter astrocytes.2006
Author(s)
Sakai K, Piao YS, Kikugawa K, Ohara S, Hasegawa M, Takano H, Fukase M, Nishizawa M, Kakita A, Takahashi H
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Journal Title
Acta Neuropathol 112
Pages: 341-348
Peer Reviewed
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[Presentation] FTLD、ALSに蓄積する異常TDP-43 の解析2008
Author(s)
長谷川成人, 新井哲明, 野中隆, 亀谷富由樹, 吉田眞理, 橋詰良夫, Beach T, 森田光哉, 中野今治, 織田辰郎, 土谷邦秋, 秋山治彦
Organizer
第27回日本認知症学会
Place of Presentation
前橋
Year and Date
2008-10-11
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[Presentation] Accumulation of phosphorylated TDP-43 in neurodegenerative disorders.2008
Author(s)
Arai T, Hasegawa M, Nonaka T, Kametani F, Ikeda K, Yoshida M, Hashizume Y, Beach TG, Buratti E, Baralle F, Morita M, Nakano I, Oda T, Tsuchiya K, Akiyama H
Organizer
International Conference on Alzheimer's Disease 2008
Place of Presentation
Chicago, USA
Year and Date
2008-07-28
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[Presentation] FTDにおけるTDP-43蓄積の意義2008
Author(s)
長谷川成人, 新井哲明, 野中隆, 亀谷富由樹, 吉田眞理, 橋詰良夫, Thomas Beach, 森田光哉, 中野今治, 織田辰郎, 土谷邦秋, 秋山治彦
Organizer
第49回日本神経学会総会
Place of Presentation
横浜
Year and Date
2008-05-17
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