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2004 Fiscal Year Final Research Report Summary

Identification of aging-related factors that facilitate Alzheimer's disease

Research Project

Project/Area Number 12210021
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 (2002-2004)
National Center of Neurology and Psychiatry (2000-2001)

Principal Investigator

TABIRA Takeshi  NATIONAL INSTITUTE FOR LONGEVITY SCIENCES, DIRECTOR GENERAL, (研究所), 研究所長 (80112332)

Co-Investigator(Kenkyū-buntansha) TANAKA Shin  ANIMAL FACILITY FOR AGING RESEARCH, NATIONAL INSTITUTE FOR LONGEVITY SCIENCES, SECTION CHIEF, 研究所, 室長 (70134624)
ARAKI Wataru  DEPARTMENT OF DEMYELINATING DISEASE AND AGING, NATIONAL INSTITUTE OF NEUROSCIENCE, SECTION CHIEF, 神経研究所, 室長 (60311429)
Project Period (FY) 2000 – 2004
KeywordsAlzheimer's disease / β amyloid / apoptosis / glypican 1 / neprilysin / aging / adoplin / AB-DIP
Research Abstract

1.We identified glypican-1 as an Aβ-binding protein. Glypican-1 was enriched in the raft fraction, and deposited in senile plaques. Glypican-1 enhanced Aβ-induced cell death.
2.By using the differential display between PS1 wild and mutant cell lines, we identified a novel protein, adoplin. Adoplin was a membrane protein, and made a complex with PS1. Over expression of adoplin enhanced Aβ production.
3.By using the yeast two-hybrid system, we identified a novel Aβ-binding protein, AB-DIP, which contained CARD and nuclear targeting sequence. Overe-xpression of AB-DIP itself induced cell death and enhanced Aβ- induced cell death.
4.Neprilysin-knock-out mice were crossed with mutant PS1-transgenic mice. The mice did not show an enhancing effect of the Alzheimer phenotype.

  • Research Products

    (38 results)

All 2005 2004 2003 2002 Other

All Journal Article (32 results) Patent(Industrial Property Rights) (6 results)

  • [Journal Article] A novel death-inducing protein, AB-DIP interacts with amyloid beta protein and mediates its neurotoxicity.2005

    • Author(s)
      Lakshmana MK, Araki W, Tabira T
    • Journal Title

      FASEB J (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Intracellular Abeta42 activates p53 promoter : a pathway to neurodegeneration in Alzheimer's disease.2004

    • Author(s)
      Ohyagi Y, Asahara H, Chui DH, Tsuruta Y, Sakae N, Miyoshi K, Yamada T, Kikuchi H, Taniwaki T, Murai H, Ikezoe K, Furuya H, Kawarabayashi T, Shoji M, Checler F, Iwaki T, Makifuchi T, Takeda K, Kira JI, Tabira T
    • Journal Title

      FASEB J 19

      Pages: 255-257

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association between tau polymorphism and male early-onset Alzheimer's disease.2004

    • Author(s)
      Tanahashi H, Asada T, Tabira T
    • Journal Title

      NeuroReport 15

      Pages: 175-180

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Enhanced generation of intracellular Aβ42 amyloid peptide by mutation of presenilins PS1 and PS2.2004

    • Author(s)
      Takeda K, Wataru A, Tabira T
    • Journal Title

      Eur J Neurosci 19

      Pages: 258-264

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Endogenous glucocorticoids are essential for maintaining prefrontal cortical cognitive function.2004

    • Author(s)
      Mizoguchi K, Ishige A, Takeda S, Aburada M, Tabira T
    • Journal Title

      J Neurosci 24

      Pages: 5492-5499

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glypican-1 as an Aβ binding HSPG in the human brain : its localization in DIG domains and possible roles in the pathogens is of Alzheimer's disease.2004

    • Author(s)
      Watanabe N, Araki W, Chui DH, Makibuchi T, Ihara Y, Tabira T
    • Journal Title

      FASEB J 18

      Pages: 1013-1015

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Development of a safe oral Abeta vaccine using recombinant adeno-associated virus vector for Alzheimer's disease.2004

    • Author(s)
      Hara H, Monsonego A, Yuasa K, Adachi K, Xiao X, Takeda S, Takahashi K, Weiner HL, Tabira T
    • Journal Title

      J Alzheim Dis 6

      Pages: 483-488

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular basis of Alzheimer's disease : From amyloid hypothesis to treatment in the foreseeable future.2004

    • Author(s)
      Tabira T
    • Journal Title

      Ger Geront Intr 4

      Pages: S27-S31

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Amino-truncated amyloid beta-peptide (Abeta5-40/42) produced from caspase-cleavedamyloidprecursorproteinisdeposited Alzmimer's disease brain.2004

    • Author(s)
      Takeda K, Araki W, Akiyama H, Tabira T
    • Journal Title

      FASEB J 18

      Pages: 1755-1757

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association between tau polymorphism and male early-onset Alzheimer's disease.2004

    • Author(s)
      Tanahashi H, Asada T, Tabira T.
    • Journal Title

      NeuroReport 15

      Pages: 175-180

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Endogenous glucocorticoids are essential for maintaining prefrontal cortical cognitive function.2004

    • Author(s)
      Mizoguchi K, Ishige A, Takeda S, Aburada M, Tabira T.
    • Journal Title

      J Neurosci 24

      Pages: 5492-5499

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Glypican-1 as an Aβ binding HSPG in the human brain : its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease.2004

    • Author(s)
      Watanabe N, Araki W, Chui DH, Makibuchi T, Ihara Y, Tabira T.
    • Journal Title

      FASEB J 18

      Pages: 1013-1015

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Development of a safe oral Abeta vaccine using recombinant adeno-associated virus vector for Alzheimer's disease.2004

    • Author(s)
      Hara H, Monsonego A, Yuasa K, Adachi K, Xiao X, Takeda S, Takahashi K, Weiner HL, Tabira T.
    • Journal Title

      J Alzheim Dis 6

      Pages: 483-488

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular basis of Alzheimer's disease : From amyloid hypothesis to treatment in the foreseeable future.2004

    • Author(s)
      Tabira T.
    • Journal Title

      Ger Geront Intr 4

      Pages: S27-S31

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Amino-truncated amyloid beta-peptide (Abeta5-40/42) produced from caspase-cleaved amyloid precursor protein is deposited in Alzheimer's disease brain.2004

    • Author(s)
      Takeda K, Araki W, Akiyama H, Tabira T.
    • Journal Title

      FASEB J 18

      Pages: 1755-1757

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Intracellular Abeta42 activates p53 promoter : a pathway to neurodegeneration in Alzheimer's disease.2004

    • Author(s)
      Ohyagi Y, Asahara H, Chui DH, Tsuruta Y, Sakae N, Miyoshi K, Yamada T, Kikuchi H, Taniwaki T, Murai H, Ikezoe K, Furuya H, Kawarabayashi T, Shoji M, Checler F, Iwaki T, Makifuchi T, Takeda K, Kira JI, Tabira T.
    • Journal Title

      FASEB J 19

      Pages: 255-257

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A clinical and pathological study of a Japanese case of amyotrophic lateral sclerosis/Parkinsonism-dementia complex with family history.2003

    • Author(s)
      Konagaya M, Kato T, Sakai M, Kuru S, Matsuoka Y, Konagaya Y, Hashizume Y, Tabira T
    • Journal Title

      J Neurol 250

      Pages: 164-170

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genetic, clinical and pathological studies of CADASIL in Japan : a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis.2003

    • Author(s)
      Santa Y, Uyama E, Chui DH, Arima M, Kotorii S, Takahashi K, Tabira T
    • Journal Title

      J Neurol Sci 212

      Pages: 79-84

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential expression of presenilin-α and -β (PSα and PSβ) in Xenopus laevis : embryonic phosphorylation of PSα.2003

    • Author(s)
      Watanabe Y, Tsujimura A, Tabira T, Hashimoto-Gotoh T
    • Journal Title

      Gene 314

      Pages: 165-172

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A unifying model for functional difference and redundancy of presenilin-1 and -2 in cell apoptosis and differentiation.2003

    • Author(s)
      Hashimoto-Gotoh T, Tsujimura A, Watanabe Y, Tabira T et al.
    • Journal Title

      Gene 323

      Pages: 115-123

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Alzheimer's disease : mechanisms and development of therapeutic strategies.2003

    • Author(s)
      Tabira T
    • Journal Title

      Geriat Geront Internat 3

      Pages: 175-188

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A clinical and pathological study of a Japanese case of amyotrophic lateral sclerosis/Parkinsonism-dementia complex with family history.2003

    • Author(s)
      Konagaya M, Kato T, Sakai M, Kuru S, Matsuoka Y, Konagaya Y, Hashizume Y, Tabira T.
    • Journal Title

      J Neurol 2003 250

      Pages: 164-170

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genetic, clinical and pathological studies of CADASIL in Japan : a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis.2003

    • Author(s)
      Santa Y, Uyama E, Chui DH, Arima M, Kotorii S, Takahashi K, Tabira T.
    • Journal Title

      J Neurol Sci 212

      Pages: 79-84

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differential expression of presenilin-α and -β (PSα and PSβ) in Xenopus laevis : embryonic phosphorylation of PSα.2003

    • Author(s)
      Watanabe Y, Tsujimura A, Tabira T, Hashimoto-Gotoh T.
    • Journal Title

      Gene 314

      Pages: 165-172

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A unifying model for functional difference and redundancy of presenilin-1 and -2 in cell apoptosis and differentiation.2003

    • Author(s)
      Hashimoto-Gotoh T, Tsujimura A, Watanabe Y, Iwabe N, Miyata T, Tabira T.
    • Journal Title

      Gene 323

      Pages: 115-123

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Alzheimer's disease : mechanisms and development of therapeutic strategies.2003

    • Author(s)
      Tabira T.
    • Journal Title

      Geriat Geront Internat 3

      Pages: 175-188

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Significance of intracellular Abeta42 accumulation in Alzheimer's disease.2002

    • Author(s)
      Tabira T, Chui DH, Kuroda S
    • Journal Title

      Front Biosci 7

      Pages: A44-A49

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] c954C>T polymorphism in the Fe65L2 gene is associated with early-onset Alzheimer's disease.2002

    • Author(s)
      Tanahashi, H, Asada T, Tabira T
    • Journal Title

      Ann Neurol 52

      Pages: 691-693

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Characterization of an amyloid precursor protein (APP)-binding protein Fe65L2 and its two novel isoforms lacking phosphotyrosine interaction domain.2002

    • Author(s)
      Tanahashi H, Tabira T
    • Journal Title

      Biochem J 367

      Pages: 687-695

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Alzheimer_s disease with spastic paresis and cotton wool type plaques.2002

    • Author(s)
      Tabira T, Chui DH, Nakayama H, Kuroda S, Shibuya M
    • Journal Title

      J Neurosci Res 70

      Pages: 367-372

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Alzheimer_s disease with spastic paresis and cotton wool type plaques.2002

    • Author(s)
      Tabira T, Chui DH, Nakayama H, Kuroda S, Shibuya M.
    • Journal Title

      J Neurosci Res 70

      Pages: 367-372

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A novel death-inducing protein, AB-DIP interacts with amyloid beta protein and mediates its neurotoxicity.

    • Author(s)
      Lakshmana MK, Araki W, Tabira T.
    • Journal Title

      FASEB J (inpress)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] Adoplinタンパク質、およびその利用2005

    • Inventor(s)
      荒木 亘, 田平 武
    • Industrial Property Rights Holder
      (財)ヒューマンサイエンス振興財団
    • Industrial Property Number
      特願2005-026405
    • Filing Date
      2005-02-02
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] アルツハイマー病治療のための組換アデノ随伴ウイルスベクター2004

    • Inventor(s)
      田平 武, 原 英夫
    • Industrial Property Rights Holder
      国立長寿医療センター, 医薬品被害救済調査審議機構
    • Industrial Property Number
      PCT/JP2004/008224
    • Filing Date
      2004-06-11
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] AB-DIP、並びにアルヅハイマー病の予防及び治療剤2004

    • Inventor(s)
      田平 武, 荒木亘, マデパリ・ケイ・ラクシュマナ
    • Industrial Property Rights Holder
      (財)ヒューマンサイエンス振興財団
    • Industrial Property Number
      特願2004-367780
    • Filing Date
      2004-12-20
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] タウ遺伝子中の遺伝子多型を利用したアルツハイマー病の発症リスクの予測法およびこれに陥るための核酸分子2003

    • Inventor(s)
      棚橋 浩, 木村英雄, 田平 武, 朝田 隆
    • Industrial Property Rights Holder
      国立精神・神経センター医薬品被害救済調査審議機構
    • Industrial Property Number
      特願2003-299939
    • Filing Date
      2003-08-25
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] アルツハイマー病治療のための組換アデノ随伴ウイルスベクター2003

    • Inventor(s)
      田平 武, 原 英夫
    • Industrial Property Rights Holder
      国立療養所中部病院太田壽城, 医薬品被害救済調査審議機構
    • Industrial Property Number
      特願2003-169-714 2003-371103
    • Filing Date
      2003-06-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] アルツハイマー病の遺伝子診断およびこれに用いるための核酸分子2002

    • Inventor(s)
      棚橋 浩, 田平 武, 朝田 隆
    • Industrial Property Rights Holder
      医薬品被害救済調査審議機構, 国立精神・神経センター ジェノックス創薬研究所
    • Industrial Property Number
      特願2002-181728
    • Filing Date
      2002-06-21
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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