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2009 Fiscal Year Final Research Report

Molecular mechanism underlying Ass assembly in Alzheimer brain : pathological and therapeutic significance of an endogenous seed for amyloid

Research Project

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Project/Area Number 17025057
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Institute for Longevity Sciences,NCGG

Principal Investigator

YANAGISAWA Katsuhiko  National Institute for Longevity Sciences,NCGG, 副所長 (10230260)

Project Period (FY) 2005 – 2009
Keywordsアルツハイマー病 / アミロイド蛋白 / ガングリオシド / アポリポ蛋白 / シナプス / マイクロドメイン / 遺伝的変異型
Research Abstract

アルツハイマー病のアミロイドss蛋白質(Ass)の重合には神経細胞膜の糖脂質であるガングリオシドに結合したAss(GAss)がアミロイドの"種"として働いていると考えられる。本研究では、GAssの形成に神経細胞内の膜輸送の障害が関わり、ガングリオシドが密集した特異な膜ドメインが形成されることが必要であることを確認した。またGAssの"種"作用の抑制により脳内におけるアミロイド形成を阻害する新しい治療法の開発を検討した。

  • Research Products

    (37 results)

All 2010 2009 2008 2007 2006 2005 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (16 results) Book (5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Surface-induced phase separation of a sphingomyelin / cholesterol / ganglioside GM1-planar bilayer on mica surfaces and microdomain molecular conformation that accelerates As oligomerization2010

    • Author(s)
      Mao Y, Zhiguo S, Imai Y, Hoshino T, Tero R, Tanaka M, Yamamoto N, Yanagisawa K, Urisu T.
    • Journal Title

      Biochim Biophys Acta (in press)

      Pages: 22-26

    • Peer Reviewed
  • [Journal Article] Gender effect on the accumulation of hyperphosphorylated tau in the brains of locus-ceruleus-injured APP transgenic mouse2010

    • Author(s)
      Oikawa N, Ogino K, Masumoto T, Yamaguchi H, Yanagisawa K.
    • Journal Title

      Neurosci. Lett. 468

      Pages: 243-247

    • Peer Reviewed
  • [Journal Article] Alzheimer-type tau pathology in advanced nonhuman primate brains harboring substantial amyloid depositio2010

    • Author(s)
      Oikawa N, Kimura N, Yanagisawa K.
    • Journal Title

      Brain. Res. 1315

      Pages: 137-149

    • Peer Reviewed
  • [Journal Article] Up-and-down topological mode of amyloid s-peptide lying on hydrophilic / hydrophobic interface of ganglioside clusters2009

    • Author(s)
      Utsumi M, Yamaguchi Y, Sasakawa H, Yamamoto N, Yanagisawa K, Kato K.
    • Journal Title

      Glycoconjugate J. 26

      Pages: 999-1006

    • Peer Reviewed
  • [Journal Article] Gangliosides determine the amyloid pathology of Alzheimer disease2009

    • Author(s)
      Oikawa N, Yamaguchi H, Ogino K, Taki T, Yuyama K, Yamamoto N, Shin R-W., Furukawa K, Yanagisawa K.
    • Journal Title

      Neuroreport 20

      Pages: 143-1046

    • Peer Reviewed
  • [Journal Article] ate endocytic dysfunction as a putative cause of amyloid fibril formation in Alzheimer's disease2009

    • Author(s)
      Yuyama K, Yanagisawa K.
    • Journal Title

      J. Neurochem 109

      Pages: 1250-1260

    • Peer Reviewed
  • [Journal Article] ate endocytic dysfunction as a putative cause of amyloid fibril formation in Alzheimer's disease2009

    • Author(s)
      Yuyama., Yanagisawa K.
    • Journal Title

      J. Neurochem 109

      Pages: 1250-1260

    • Peer Reviewed
  • [Journal Article] ccelerated release of exosome-associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1-induced amyloid fibril formation2008

    • Author(s)
      Yuyama K, Yamamoto N, Yanagisawa K.
    • Journal Title

      J. Neurochem 105

      Pages: 217-224

    • Peer Reviewed
  • [Journal Article] Age-dependent high-density clustering of GM1 ganglioside at presynaptic neuritic terminals promotes amyloid s-protein fibrillogenesis2008

    • Author(s)
      Yamamoto N, Matusbara T, Sato T. Yanagisawa K.
    • Journal Title

      Biochim. Biophys. Acta 1778

      Pages: 2717-2726

    • Peer Reviewed
  • [Journal Article] A ganglioside -induced toxic soluble As assembly: Its enhanced formation from As bearing theArctic mutation2007

    • Author(s)
      amamoto N, Matsubara E, Maeda S, Minagawa H, Takashima A, Maruyama W, Michikawa M, Yanagisawa, K.
    • Journal Title

      J. Biol. Chem 282

      Pages: 2646-2656

    • Peer Reviewed
  • [Journal Article] GM1-ganglioside-induced As assembly on synaptic membranes of cultured neurons2007

    • Author(s)
      Yamamoto N, Fukata Y, Fukata M, Yanagisawa K.
    • Journal Title

      Biochim. Biophys. Acta 1768

      Pages: 1128-1137

    • Peer Reviewed
  • [Journal Article] Chloroquine-induced endocytic pathway abnormalities: cellular model of GM1 -ganglioside-induced As fibrillogenesis in Alzheimer's disease2006

    • Author(s)
      Yuyama K, Yamamoto N, Yanagisawa K.
    • Journal Title

      FEBS Lett 580

      Pages: 6972-6976

    • Peer Reviewed
  • [Journal Article] Assembly of hereditary amyloid s-protein variants in the presence of favorable gangliosides2005

    • Author(s)
      Yamamoto N, Hirabayashi Y, Amari M, Yamaguchi H, Romanov G, Van Nostr, W.E., Yanagisawa K.
    • Journal Title

      FEBS Lett 579

      Pages: 2185-2190

    • Peer Reviewed
  • [Journal Article] Cross seeding of wild- and hereditary variant-type amyloid s-proteins in the presence of gangliosides2005

    • Author(s)
      Yamamoto N, Matsuzaki K, Yanagisawa K.
    • Journal Title

      J. Neurochem. 95

      Pages: 1167-1176

    • Peer Reviewed
  • [Journal Article] Suppression of As deposition in brain by peripheral administration of Fab fragments of anti-seed antibody2005

    • Author(s)
      Yamamoto N, Yokoseki T, Shibata M, Yamaguchi H, Yanagisawa K.
    • Journal Title

      Biochem. Biophys. Res. Commun. 335

      Pages: 45-47

    • Peer Reviewed
  • [Presentation] Lipid metabolism and its pathophysiology in CNS2009

    • Author(s)
      シンポジウム
    • Organizer
      第51回日本脂質生化学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-07-30
  • [Presentation] アルツハイマー病におけるGM1ガングリオシド誘導性アミロイドs蛋白質重合に関与する後期エンドサイトーシス障害2009

    • Author(s)
      湯山耕平, 柳澤勝彦
    • Organizer
      第52回日本神経化学会大会
    • Place of Presentation
      渋川
    • Year and Date
      2009-06-22
  • [Presentation] カニクイザル脳におけるアルツハイマー病関連蛋白(As、タウ)の解析2008

    • Author(s)
      及川尚人, 木村展之, 柳澤勝彦
    • Organizer
      第27回日本認知症学会
    • Place of Presentation
      前橋
    • Year and Date
      2008-10-11
  • [Presentation] As線維化に関与するGM1ガングリオシド集積を誘導するエンドサイトーシス経路障害2008

    • Author(s)
      湯山耕平, 山本直樹, 柳澤勝彦
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山
    • Year and Date
      2008-09-21
  • [Presentation] シナプス前膜の年齢依存的なGM1 ganglioisde集積ドメイン形成はAs線維化を促す2008

    • Author(s)
      山本直樹, 松原輝彦, 湯山耕平, 佐藤智典, 柳澤勝彦
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山
    • Year and Date
      2008-09-12
  • [Presentation] A ganglioside-induced soluble As assembly causes neuronal death through NGF receptors2007

    • Author(s)
      Yamamoto N, Matsubara E, Maeda S, Minagawa H, Takashima A, Michikawa M, Yanagisawa K.
    • Organizer
      37th Society for Neuroscience Annual Meeting
    • Place of Presentation
      サンディエゴ, アメリカ
    • Year and Date
      2007-11-05
  • [Presentation] エンドサイトーシス経路異常によるGM1ガングリオシドの細胞外放出の促進2007

    • Author(s)
      湯山耕平, 山本直樹, 柳澤勝彦
    • Organizer
      第50回日本神経化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-09-10
  • [Presentation] 老齢マウス脳シナプス膜中の特異なGM1 ganglioside集積ドメイン2007

    • Author(s)
      山本直樹, 湯山耕平, 柳澤勝彦
    • Organizer
      50回日本神経化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-09-10
  • [Presentation] A ganglioside-induced toxic soluble As assemblycauses neuronal death2006

    • Author(s)
      山本直樹, 松原悦朗, 前田純裕, 高島明彦, 丸山和佳子, 道川誠, 柳澤勝彦
    • Organizer
      第29回日本分子生物学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2006-12-06
  • [Presentation] GM1-ganglioside-induced As assembly at neuritic terminals of nerve growth factor-treated PC12 cells2006

    • Author(s)
      山本直樹, 湯山耕平, 柳澤勝彦
    • Organizer
      第49回日本神経化学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2006-09-14
  • [Presentation] GM1 ganglioside accumulation in PC12 cells treated with chloroquine: a cellular model of As assembly2006

    • Author(s)
      湯山耕平, 山本直樹, 柳澤勝彦
    • Organizer
      第49回日本神経化学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2006-09-14
  • [Presentation] Pivotal roles of lipids in generating an endogenous seed for Alzheimer amyloid2005

    • Author(s)
      Yanagisawa K.
    • Organizer
      7th International Conference on Alzheimer's Disease and Parkinson Disease. Sorrento
    • Place of Presentation
      イタリア
    • Year and Date
      20050509-20050514
  • [Presentation] 膜マイクロドメインとアルツハイマー病:GM1ガングリオシド集積の意味2005

    • Author(s)
      柳澤勝彦
    • Organizer
      第28回日本分子生物学会
    • Place of Presentation
      福岡
    • Year and Date
      2005-12-10
  • [Presentation] Assembly of hereditary variant amyloid s-protein in the presence of gangliosides2005

    • Author(s)
      Yamamoto N, Hirabayashi Y, Amari M, Yamaguchi H, Romanov G, Nostr, W, Yanagisawa K.
    • Organizer
      第48回日本神経化学会
    • Place of Presentation
      福岡
    • Year and Date
      2005-09-28
  • [Presentation] アミロイドs蛋白重合とガングリオシド2005

    • Author(s)
      柳澤勝彦
    • Organizer
      第28回日本神経科学大会シンポジウム「糖鎖科学と神経科学の融合による新展開」
    • Place of Presentation
      横浜
    • Year and Date
      2005-07-27
  • [Presentation] Pathological significance of ganglioside cluster in Alzheimer disesse

    • Author(s)
      柳澤勝彦
  • [Book] Research Progress in Alzheimer's Disease(edited by Miao-Kun Sun, Pivotal roles of cholesterol and gangliosides in aggregation of amyloid β-protein.)2010

    • Author(s)
      Yanagisawa K.
    • Publisher
      Nova Science Pulishers, Inc.(in press)
  • [Book] Comprehensive Glycoscience(edited by Kamerling J.P., Boons G-J., Lee Y.C.,Suzuki A. and Taniguchi N., Glycoconjugates and neurological diseases.)2007

    • Author(s)
      Yanagisawa K, Yuki N.
    • Total Pages
      495-513
    • Publisher
      Elsevier
  • [Book] Sphingolipid Biology.(edited by Hirabayashi Y, Igarashi Y and Merill AH, Ganglioside and Alzheimer's disease.)2006

    • Author(s)
      Yanagisawa K.
    • Total Pages
      309-317
    • Publisher
      Springer
  • [Book] Recent Progress in Alzheimer's and Parkinsons's Diseases(edited by Hanin I,Casabelos R and Fisher A, Cholesterol and Aβ cascade:pathological implication of apolipoprotein E in Alzheimer's disease.)2005

    • Author(s)
      Yanagisawa K.
    • Total Pages
      133-137
    • Publisher
      Taylor & Francis
  • [Book] Cholesterol and amyloid β fibrillogenesisIn: Alzheimer's Disease: Cellular and Molecular Aspects of Amyloid β(edited by Robin Harris and Falk Fahrenholz)2005

    • Author(s)
      Yanagisawa, K.
    • Total Pages
      179-202
    • Publisher
      Springer-Verlag
  • [Patent(Industrial Property Rights)] 可溶性アミロイドs蛋白重合体の調整法ならびに毒性評価法2006

    • Inventor(s)
      柳澤勝彦、山本直樹
    • Industrial Property Rights Holder
      ヒューマンサイエンス振興財団
    • Industrial Property Number
      特許権
    • Filing Date
      2006-06-05

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Published: 2011-06-18   Modified: 2016-04-21  

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