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Involvement of protein s coded by causative genes for familial dementia and ubiquitin system in neurodegenerative mechanisms

Research Project

Project/Area Number 19390305
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionOsaka University

Principal Investigator

TAKEDA Masatoshi  Osaka University, 医学系研究科, 教授 (00179649)

Co-Investigator(Kenkyū-buntansha) TANAKA Toshihisa  大阪大学, 医学系研究科, 講師 (10294068)
KUDO Takashi  大阪大学, 医学系研究科, 准教授 (10273632)
MORIHARA Takashi  大阪大学, 医学系研究科, 助教 (90403196)
Research Collaborator GOLAM Sadik  大阪大学, 医学系研究科, 特任研究員
YANAGI Kentaro  大阪大学, 医学系研究科, 大学院生
KATO Kiyoko  大阪大学, 医学系研究科, 大学院生
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2008: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2007: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Keywords前頭側頭型認知症 / 神経変性 / タウ蛋白 / ユビキチン / プロテオソーム / 蛋白分解
Research Abstract

タウ蛋白分解機構にユビキチンシステムがどのように関与しているかに関して検討をおこなうため、培養細胞にプロテアーゼに対する各阻害剤を添加してタウ蛋白の分解過程の検討をおこなったところ、ピューロマイシンのみに分解抑制効果が認められた。さらに、FTDP-17にて報告されたV337MとR406W変異タウに関して検討をおこなったところ、分解の遅延が認められた。ピューロマイシン感受性ペプチダーゼと強制発現タウはどちらも細胞質内に局在し、変異タウ蛋白はリン酸化が亢進していたことより、変異タウの分解遅延はリン酸化亢進にともなうプロテアーゼ抵抗性によることが示唆された。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (48 results)

All 2009 2008 2007

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (25 results) Book (1 results)

  • [Journal Article] Involvement of puromycine-sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of FTDP-17 mutant tau2009

    • Author(s)
      Yanagi K, Tanaka T, Kato K, Sadik G, Morihara T, Kudo T, Takeda M
    • Journal Title

      Psycogeriatrics (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential interaction and aggregation of 3-repeat and 4-repeat tau isoforms with 14-3-3zeta protein2009

    • Author(s)
      Sadik G, Tanaka T., Kato K, Yanagi K, Kudo T, Takeda M
    • Journal Title

      Biochem Biophys Res Commun 383(1)

      Pages: 37-41

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein : Implications for the mechanism of tau aggregation2009

    • Author(s)
      Sadik G, Tanaka T., Kato K, Yanagi K, Morihara T, Takeda M
    • Journal Title

      J Neurochem 108

      Pages: 33-34

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein : implications for the mechanism of tau aggregation.2009

    • Author(s)
      Sadik G, Tanaka T, Kato K, Yamamori H, Nessa BN, Morihara T, Takeda M.
    • Journal Title

      J Neurochem 108

      Pages: 33-43

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decrease of dynamin 2 levels in late-onset Alzheimer's disease alters Abeta metabolism2009

    • Author(s)
      Kamagata E, Kudo T, Kimura R, Tanimukai H, Morihara T, Sadik G, Kamino K, Takeda M.
    • Journal Title

      Biochem Biophys Res Commun (未定)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of puromycin -sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of FTDP-17 mutant tau.2009

    • Author(s)
      Yanagi K, Tanaka T, Kato K, Sadik G, Morihara T, Takeda M.
    • Journal Title

      Psycogeriatrics 9(未定)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mild Cognitive Impairment (MCI) and Subjective Cognitive Impairment (SCI)2008

    • Author(s)
      Takeda M, Morihara T, Okochi M, Sadik G, Tanaka T
    • Journal Title

      Psycogeriatrics 8

      Pages: 155-160

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dynamin 2 gene is a novel susceptibility gene for late-onset Alzheimer disease in non-APOE-epsilon4 carriers2008

    • Author(s)
      Aidaralieva NJ, Kamino K, Kimura R, Yamamoto M, Morihara T, Kazui H, Hashimoto R, Tanaka T, Kudo T, Kida T, Okuda J, Uema T, Yamagata H, Miki T, Akatsu H, Kosaka K, Takeda M.
    • Journal Title

      J Hum Genet 53

      Pages: 296-302

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Post-marketing surveillance of donepezil hydrochloride in Japanese patients with Alzheimer's disease with behavioral and psychological symptoms of dementia (BPSD)2008

    • Author(s)
      Tanaka T., Kazui H., Tanimukai H., Morihara H., Sadik G., Kudo T., Takeda M.
    • Journal Title

      Psycogeriatrics 8

      Pages: 114-123

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Processes of β-amyloid and intracellular cytoplasmic domain generation by presenilin/γ-Secretase2008

    • Author(s)
      Tagami S., Okochi M., Fukumori A., Jingwei J., Yanagida K., Nakayama T., Morihara T., Tanaka T., Kudo T., Takeda M.
    • Journal Title

      Neurodegenerative Dis. 5

      Pages: 160-162

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Notch signaling by dynamic changes in the precision in S3 cleavage of Notch-12008

    • Author(s)
      Tagami S., Okochi M., Yanagida K., Ikuta A., Fukumori A., Matsumoto N., Ishizuka-Katsura Y., Nakayama T., Ito N., Jiang J., Nishitomi K., Kamino K., Morihara T., Hashimoto R., Tanaka T., Kudo T., Chiba S., Takeda M.
    • Journal Title

      Mol Cell Biol 28

      Pages: 165-176

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The 13th congress of IPA and recent expansion of researches into psychogeriatric2008

    • Author(s)
      Tanaka T., Tomioka M., Sadik G, Takeda M.
    • Journal Title

      Psycogeriatrics 8

      Pages: 1-3

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Post-marketing surveillance of donepezil hydrochloride in Japanese patients with Alzheimer's disease with behavioral and psychological symptoms of dementia(BPSD).2008

    • Author(s)
      Tanaka T., Kazui H., Tanimukai H., Morihara H., Sadik G., Kudo T., Takeda M.
    • Journal Title

      Psycogeriatrics 8

      Pages: 114-123

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mild Cognitive Impairment (MCI)and Subjective Cognitive Impairment (SCI)2008

    • Author(s)
      Takeda M, Morihara T, Okochi M, Sadik G, Tanaka T
    • Journal Title

      Psycogeriatrics 8

      Pages: 155-160

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Processes of beta-amyloid and intracellular cytoplasmic domain generation bypresenilin/gamma-secretase.2008

    • Author(s)
      Tagami s, Okochi M, Fukumori A, Jiang J, Yanagida K, Nakayama T, Morihara T, Tanaka T, Kudo T, Takeda M.
    • Journal Title

      Neurodegener Dis 5

      Pages: 160-162

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between quality of life of demented patients and professionalknowledge of care workers.2008

    • Author(s)
      Kazui H, Harada K, Eguchi YS, Tokunaga H, Endo H, Takeda M. J
    • Journal Title

      Geriatr Psychiatry Neurol 21

      Pages: 72-78

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Event-related synchronization of alpha activity in early Alzheimer's disease and mild cognitive impairment : an MEG study combining beamformer and groupcomparison.2008

    • Author(s)
      Kurimoto R, Ishii R, Canuet L, Ikezawa K, Azechi M, Iwase M, Yoshida T, Kazui H, Yoshimine T, Takeda M.
    • Journal Title

      Neurosci Lett 443

      Pages: 86-89

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biological markers as outcome measures for Alzheimer's disease interventions-real problems and future possibilities2007

    • Author(s)
      Takeda M, Okochi M, Tagami S, Tanaka T, Kudo T.
    • Journal Title

      Int Psychogeriatr 19

      Pages: 391-400

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between {beta}-amyloid production and tau phosphorylation in Alzheimer disease2007

    • Author(s)
      R, Tanaka T, Kudo T, Yamagata H, Tabara Y, Miki T, Akatsu H, Kosaka K, Funakoshi E, Nishitomi K, Sakaguchi G, Kato A, Hattori H, Uema T, Takeda M.
    • Journal Title

      Hum Mol Genet 16

      Pages: 15-23

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biological markers as outcome measures for Alzheimer's disease interventions-real problems and future possibilities.2007

    • Author(s)
      Takeda M, Okochi M, Tagami S, Tanaka T, Kudo T.
    • Journal Title

      Int Psychogeriatr. 19

      Pages: 391-400

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between{beta}-amyloid production and tau phosphorylation in Alzheimer disease.2007

    • Author(s)
      Kimura R, Kamino K, Yamamoto M, Nuripa A, Kida T, Kazui H, Hashimoto R Tanaka T, Kudo T, Yamagata H, Tabara Y, Miki T, Akatsu H, Kosaka K, Funakoshi E, Nishitomi K, Sakaguchi G, Kato A, Hattori H, Uema T, Takeda M
    • Journal Title

      Hum Mol Genet 16

      Pages: 15-23

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Notch signaling by dynamic changes in the precision in S3 cleavage of Notch-1.2007

    • Author(s)
      Tagami S., Okochi M., Yanagida K., Ikuta A., Fukumori A., Matsumoto Nishizuka-Katsura Y., Nakayama T., Ito N., Jiang J., Nishitomi K., Kamino K., Morihara T., Hashimoto R., Tanaka T., Kudo T., Chiba S., Takeda M.
    • Journal Title

      Mol Cell Biol 28

      Pages: 165-176

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 14-3-3 Protein is a potential candidate inducer for fibrillization of 3-repeat2008

    • Author(s)
      Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
    • Organizer
      Tau Soociety for Neuroscience the 38^<th> Annual Meeting
    • Place of Presentation
      Washington, U.S.A.
    • Related Report
      2008 Final Research Report
  • [Presentation] GSK3抑制によるカスペース阻害因子XIAPの亢進機序について2008

    • Author(s)
      加藤希世子、田中稔久、Golam Sadik, 柳健太郎、武田雅俊
    • Organizer
      第27回日本認知症学会
    • Place of Presentation
      群馬県前橋市
    • Related Report
      2008 Final Research Report
  • [Presentation] Involvement of tau protein in neurodegeneration2008

    • Author(s)
      Tanaka T, Sadik G, Kato K, Yanagi K, Takeda M
    • Organizer
      第51回日本神経化学大会
    • Place of Presentation
      富山
    • Related Report
      2008 Final Research Report
  • [Presentation] 14-3-3 differentially induces 3-repeat and 4-repeat tau aggregation2008

    • Author(s)
      Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
    • Organizer
      第51回日本神経化学大会
    • Place of Presentation
      富山
    • Related Report
      2008 Final Research Report
  • [Presentation] 14-3-3 Protein Exhibits Strong Affinity for 3-repeat Tau and Increases Its Filament Formation2008

    • Author(s)
      Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
    • Organizer
      The 11^<th> international conference on Alzheimer disease and related disorders
    • Place of Presentation
      Chicago, U.S.A.
    • Related Report
      2008 Final Research Report
  • [Presentation] 14-3-3 Protein Exhibits Strong Affinity for 3-repeat Tau and Increases Its Filament Formation2008

    • Author(s)
      Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
    • Organizer
      The 11th international conference on Alzheimerdisease and related disorders
    • Place of Presentation
      Chicago USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Drastic Impact on Abeta Accumulation in APP Tg Mice By Genetic Background.2008

    • Author(s)
      Morihara T, Yokokoji M, Hayashi N, Noshi E, Mori K, Tagami S, Kudo T, Kamino K, Taked M
    • Organizer
      The 11th international conference on Alzheimerdisease and related disorders
    • Place of Presentation
      Chicago USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Involvement of tau protein in neurodegeneration2008

    • Author(s)
      Tanaka T, Sadik G, Kato K, Yanagi K, Takeda M
    • Organizer
      第51回神経化学大会
    • Place of Presentation
      富山
    • Related Report
      2008 Annual Research Report
  • [Presentation] 14-3-3 differentially induces 3-repeat and 4-repeat tau aggregation2008

    • Author(s)
      Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
    • Organizer
      第51回神経化学大会
    • Place of Presentation
      富山
    • Related Report
      2008 Annual Research Report
  • [Presentation] Risk Genes for Dementia2008

    • Author(s)
      森原剛史, 紙野晃人, 数井裕光, 林紀行, 横小路美貴子, 工藤喬, 武田雅俊
    • Organizer
      第51回神経化学大会
    • Place of Presentation
      富山
    • Related Report
      2008 Annual Research Report
  • [Presentation] アルツハイマー病モデルマウス(APP Tg)のアミロイド病理は背景遺伝子で大きく変わる2008

    • Author(s)
      横小路美貴子, 森原剛史, 林紀行田上真次, 武田雅俊
    • Organizer
      第51回神経化学大会
    • Place of Presentation
      富山
    • Related Report
      2008 Annual Research Report
  • [Presentation] GSK3抑制によるカスベース阻害因子XIAPの亢進機序について2008

    • Author(s)
      加藤希世子, 田中稔久, Golam Sadik, 柳健太郎, 武田雅俊
    • Organizer
      第27回日本認知症学会学術集会
    • Place of Presentation
      前橋
    • Related Report
      2008 Annual Research Report
  • [Presentation] APP TgマウスのAβ蓄積量はマウス背景遺伝子の違いで大きく変わる2008

    • Author(s)
      森原剛史, 横小路美貴子, 林紀行, 田上真次, 工藤喬, 熨斗英理子, 伊藤尚弘, 西富晃平, 武田雅俊
    • Organizer
      第27回日本認知症学会学術集会
    • Place of Presentation
      前橋
    • Related Report
      2008 Annual Research Report
  • [Presentation] 14-3-3 Protein Exhibits Strong Affinity for 3-repeat Tau and Increases Its Filament Formation2008

    • Author(s)
      Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
    • Organizer
      Soociety for Neuroscience the 38th Annual Meeting
    • Place of Presentation
      Washington, U. S. A.
    • Related Report
      2008 Annual Research Report
  • [Presentation] Genetic approaches in Dmentia Study2007

    • Author(s)
      Tanaka T, Kamino K, Morihara T, Sadik G, Kimura R, Kudo T, Takeda M.
    • Organizer
      Japan-Taiwan Dementia Symposium
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2007-10-13
    • Related Report
      2008 Final Research Report
  • [Presentation] FTDP-17 mutations of tau affect the interaction between tau and 14-3-32007

    • Author(s)
      Sadik G, Tanaka T, Kato K, Takeda M
    • Organizer
      Soociety for Neuroscience the 37^<th> Annual Meeting
    • Place of Presentation
      San Diego, U.S.A.
    • Related Report
      2008 Final Research Report
  • [Presentation] Symposium S34, Prevention, early diagnosis and treatment of dementia2007

    • Author(s)
      Tanaka T, Kazui H, Morihara T, Kamino K, Okochi M, Tagami S, Kudo T, Takeda M.
    • Organizer
      The 13^<th> Congress of the International Psychogeriatrics Association
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Increased expression of Toll like receptor 3 in Alzheimer disease brain2007

    • Author(s)
      Tanaka T, Nessa BN, Sadik G, Kato K, Takeda M.
    • Organizer
      The 13^<th> Congress of the International Psychogeriatrics Association
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Toll like receptor 3 mediated pathogenesis in Alzheimer's disease2007

    • Author(s)
      Nessa BN, Tanaka T, Kamino K, Sadik G, Ansar AB, Kudo T, Takeda M.
    • Organizer
      The 13^<th> Congress of the International Psychogeriatrics Association
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Phosphorylation of tau with or without FTDP-17 mutations similarly affects the interaction with 14-3-3 protein2007

    • Author(s)
      Sadik G, Tanaka T, Kato K, Takeda M
    • Organizer
      The 13^<th> Congress of the International Psychogeriatrics Association
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Neuroprotective effects of lithium2007

    • Author(s)
      Kato K, Tanaka T, Sadik G, Takeda M.
    • Organizer
      The 13^<th> Congress of the International Psychogeriatrics Association
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Degradation of tau protein in cultured cells2007

    • Author(s)
      Yanagi K, Tanaka T, Sadik G, Kato K, Takeda M.
    • Organizer
      The 13^<th> Congress of the International Psychogeriatrics Association
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] γSecretase inhibitors DAPT and L-685,458 perturb Wnt signaling2007

    • Author(s)
      Nakayama T, Okochi M, Tagami S, Yanagida K, Nishitomi K, Oguri T, Jiang J, Mori K, Morihara T, Hashimoto R, Tanaka T, Kudo T, Takeda M.
    • Organizer
      The 13^<th> Congress of the International Psychogeriatrics Association
    • Place of Presentation
      Osaka, Japan.
    • Related Report
      2008 Final Research Report
  • [Presentation] FTDP-17 mutations of tau affect the interaction between tau and 14-3-32007

    • Author(s)
      Sadik G, Tanaka T, Kato K Takeda M
    • Organizer
      Soociety for Neuroscience, the 37th Annual Meeting
    • Place of Presentation
      San Diego, U.S.A.
    • Related Report
      2007 Annual Research Report
  • [Presentation] Prevention, early diagnosis and treatment of dementia.2007

    • Author(s)
      Tanaka T, Kazui H, Morihara T, Kamino K, Okochi M, Tagami S, Kudo T, Takeda M.
    • Organizer
      The 13th Congress of the International Psychogeriatrics Association
    • Place of Presentation
      Osaka, Japan.
    • Related Report
      2007 Annual Research Report
  • [Book] タウオパチー、KEY WORD 精神 第4版2007

    • Author(s)
      田中稔久、武田雅俊
    • Publisher
      先端医学社(東京)
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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