• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular and cell biological studies on the production, aggregation and clearance of Alzheimer amyloid β peptides.

Research Project

Project/Area Number 17200025
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

IWATSYBO Takeshi  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor (50223409)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Tadafumi  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Assistant Professor (30334337)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥46,670,000 (Direct Cost: ¥35,900,000、Indirect Cost: ¥10,770,000)
Fiscal Year 2007: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2006: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2005: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
KeywordsAlzheimer's disease / γ-Secretase / Amyloid / amyloid binding protein / Aβ / アルツハイマー病 / βアミロイド
Research Abstract

The aim of this research project is to elucidate the process of production, accumulation and clearance of amyloid β peptides, that are regarded as pathogenic proteins in Alzheimer's disease (AD), thereby creating a novel concept for the disease-modifying therapy for AD. Through the studies of γ-secretase, a membrane protease that produces Aβ peptide, we tried to clarify the mechanism of Aβ production and to block the most upstream cause of AD. Specifically we developed novel γ-secretase inhibitors harboring an enone-moiety and analyzed the mechanism of action of these compounds. Using Cys scan approach, we showed that the 6/7 transmembrane domains of presenilin 1, the latter being the catalytic subunit of γ-secretase, form a hydrophilic catalytic pore structure, We further analyzed the structure of γ-secretase and a related protease, SPP, using single particle analysis. We showed that CLAC, a novel amyloid plaque component protein, inhibits Aβ fibril formation in vitro, and is involved in the compaction of amyloid plaques in the brains of transgenic mice. We also showed that LRP1 is involved in the clearance of All peptides across the blood brain barrier, using an immortalized cell line of brain endothelial cells. We thus elucidated the key steps of Aβ deposition, i.e., γ-secretase, amyloid binding protein and Aβ clearance, using cutting edge technologies including proteomic analysis, RNAi and small molecule screen, providing clues to the development of novel therapeutic strategies for AD.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (91 results)

All 2008 2007 2006 2005 Other

All Journal Article (55 results) (of which Peer Reviewed: 29 results) Presentation (35 results) Remarks (1 results)

  • [Journal Article] Both Notchl and Notch2 contribute to the regulation of melanocyteho meostasis2008

    • Author(s)
      Kumano K, et. al.
    • Journal Title

      Pigment Cell & Melanoma Research 21

      Pages: 70-78

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ATP-binding cassette transporter Al(ABCA1) deficiency does not attenuate the brain-to-blood efflux transport of human amyloid-β peptide(1-40) at the blood-brain barrier2008

    • Author(s)
      Akanuma SI, et. al.
    • Journal Title

      Neurochem Int 52

      Pages: 956-961

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aβ42 overproduction associated with structural changes in the catalytic pore of γ-secretase: common effects of Pen-2 amino-terminal elongation and fenofibrate.2007

    • Author(s)
      Isoo N
    • Journal Title

      J Biol Chem 282

      Pages: 12388-12396

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic γ-secretase inhibitors.2007

    • Author(s)
      Fuwa H
    • Journal Title

      ACS Chem Biol 2

      Pages: 408-418

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The Tottori (D7N) and English (H6R) familial Alzheimer's disease mutations accelerate A β fibril formation without increasing protofibril formation.2007

    • Author(s)
      Hori Y
    • Journal Title

      J Biol Chem 282

      Pages: 4916-4923

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Convenient synthesis of photoaffinity probes and evaluation of their cross-linking abilities2007

    • Author(s)
      Kan T^*, Kita Y, Morohashi Y, Tominari Y, Hosoda S, Tomita T, Natsugari H, Iwatsubo T, Fukuyama T
    • Journal Title

      Org lett 9

      Pages: 2055-2058

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Aβ42 overproduction associated with structural changes in the catalytic pore of γ-secretase : common effects of Pen-2 amino-terminal elongation and fenofibrate2007

    • Author(s)
      Isoo N, Sato C, Miyashita H, Shinohara M, Takasugi N, Morohashi Y, Tsuji S, Tomita T^*, Iwatsubo T^*
    • Journal Title

      J Biol Chem 282

      Pages: 12388-12396

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic γ-secretase inhibitors2007

    • Author(s)
      Fuwa H^*, Konno Y, Takahashi Y, Sasaki M, Yokoshima S, Kan T, Fukuyama T, Natsugari H, Tomita T^*, Iwatsubo T
    • Journal Title

      ACS Chem Biol 2

      Pages: 408-418

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Tottori (D7N) and English (H6R) familial Alzheimer's disease mutations accelerate All fibril formation without increasing protofibril formation2007

    • Author(s)
      Hori Y, Hashimoto T, Wakutani Y, Urakami K, Nakashima K, Condron MM, Tsubuki S, Saido TC, Teplow DB, Iwatsubo T
    • Journal Title

      J Biol Chem 282

      Pages: 4916-4923

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Tottori (D7N) and English (H6R) familial Alzheimer's disease mutations accelerate Aβ fibril formation without increasing protofibril formation2007

    • Author(s)
      Hori Y, et. al.
    • Journal Title

      The Journal of Biological Chemistry 282

      Pages: 4916-4923

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aβ42 overproduction associated with structural changes in the catalytic pore of γ-secretase: common effects of Pen-2 amino-terminal elongation and fenofibrate2007

    • Author(s)
      Isoo N, et. al.
    • Journal Title

      The Journal of Biological Chemistry 282

      Pages: 12388-12396

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Space-occupying plaques in PS-1 C410Y Alzheimer's disease contain synaptic- terminal specific proteins2007

    • Author(s)
      Haleem K, et. al.
    • Journal Title

      American Journal of Alzheimer's Disease 22

      Pages: 137-144

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Convenient synthesis of photoaffinity probes and evaluation of their labeling abilities2007

    • Author(s)
      Kan T, et. al.
    • Journal Title

      Org Lett 9

      Pages: 2055-2058

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic γ-secretase inhibitors2007

    • Author(s)
      Fuwa H, et. al.
    • Journal Title

      ACS Chemical Biology 2

      Pages: 408-418

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analytical method for β-amyloid fibrils using CE-laser induced fluore scence and its application to screening for inhibitors of β-amyloid protein aggregation2007

    • Author(s)
      Kato M, et. al.
    • Journal Title

      Anal Chem 79

      Pages: 4887-4891

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced accumulation of phosphorylated α-synuclein and elevated Aβ42/40 ratio caused by expression of the presenilin-1 △T440 mutant associated with familial Lewy body disease and variant Alzheimer disease2007

    • Author(s)
      Kaneko H, et. al.
    • Journal Title

      J Neurosci 27

      Pages: 13092-13

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunoreactivity of phage library-derived human single-chain antibodies to amyloid β conformers in vitro2007

    • Author(s)
      Yoshihara T, et. al.
    • Journal Title

      J Biochem 143

      Pages: 475-486

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Tottori (D7N) and English (H6R) familial Alzheimer's disease mutations accelerate A βfibril formation without increasing protofibril formation.2007

    • Author(s)
      Hori Y
    • Journal Title

      J Biol Chem 282

      Pages: 49164923-49164923

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Three-dimensional structure of the γ-secretase complex.2006

    • Author(s)
      Ogura T
    • Journal Title

      Biochem Biophys Res Comm 343

      Pages: 325-343

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Carboxyl-terminal fragment of presenilin is the molecular target of a dipeptidic γ-secretase-specific inhibitor DAPT.2006

    • Author(s)
      Morohashi Y
    • Journal Title

      J Biol Chem 281

      Pages: 14670-14676

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Presenilin-dependent intramembrane cleavage of ephrin-B12006

    • Author(s)
      Tomita T
    • Journal Title

      Mol Neurodegener 1

      Pages: 2-2

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Novel γ-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates.2006

    • Author(s)
      Takahashi Y
    • Journal Title

      Bioorg Med Chem Lett 16

      Pages: 3813-3816

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Naphthyl and coumarinyl biarylpiperazine derivatives as highly potent human β-secretase inhibitors. Design, synthesis, enzymatic BACE-1 and cell assays.2006

    • Author(s)
      Garino C
    • Journal Title

      J Med Chem 49

      Pages: 4725-4285

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Synthesis of biotinylated photoaffinity probes based on arylsulfonamide γ-secretase inhibitors.2006

    • Author(s)
      Fuwa H
    • Journal Title

      Bioorg Med Chem Lett 16

      Pages: 4184-4189

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis.2006

    • Author(s)
      Ozaki T
    • Journal Title

      Biochem Biophys Res Comm 351

      Pages: 57-63

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Structure of the catalytic pore of γ-secretase probed by the accessibility of substituted cysteines.2006

    • Author(s)
      Sato C
    • Journal Title

      J Neurosci 26

      Pages: 12081-12088

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Concise and short synthesis of functionalized 5,6-Dihydropyridin-2-ones by means of palladium(0)-catalyzed cross-coupling of ketene aminal phosphates.2006

    • Author(s)
      Fuwa H
    • Journal Title

      Heterocycles 70

      Pages: 101-106

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid β-peptide by the liver.2006

    • Author(s)
      Tamaki C
    • Journal Title

      Pharmaceut Res 23

      Pages: 1407-1416

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Convenient synthesis of photoaffinity probes and evaluation of their cross-linking abilities.2006

    • Author(s)
      Kan T
    • Journal Title

      Org lett 9

      Pages: 2055-2058

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Three-dimensional structure of the γ-secretase complex2006

    • Author(s)
      Ogura T, Mio K, Hayashi I, Miyashita H, Fukuda R, Kopan R, Kodama T, Hamakubo T, Iwatsubo T, Tomita T^*, Sato C^*
    • Journal Title

      Biochem Biophys Res Comm 343

      Pages: 525-534

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] C-terminal fragment of Presenilin is the molecular target of a dipeptidic γ-secretase-specific Inhibitor DAPT2006

    • Author(s)
      Morohashi Y, Kan T, Tominari Y, Fuwa H, Okamura Y, Watanabe N, Sato C, Natsugari H, Fukuyama T, Iwatsubo T^*, Tomita T^*
    • Journal Title

      J Biol Chem 281

      Pages: 14670-14676

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Presenilin-dependent intramembrane cleavage of ephrin-B12006

    • Author(s)
      Tomita T^*, Tanaka S, Morohashi Y, Iwatsubo T^*
    • Journal Title

      Molecular Neurodegeneration 1

      Pages: 2-2

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Novel γ-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates2006

    • Author(s)
      Takahashi Y, Fuwa H, Kaneko A, Sasaki M, Yokoshima S, Koizumi H, Takebe T, Kan T, Iwatsubo T^*, Tomita T, Natsugari H^*, Fukuyama T
    • Journal Title

      Bioorg Med Chem Lett 16

      Pages: 3813-3816

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Naphthyl and coumarinyl biarylpiperazine derivatives as highly potent human β-secretase inhibitors. Design, synthesis, enzymatic BACE-1 and cell assays2006

    • Author(s)
      Garino C, Tomita T, Pietrancosta N, Laras Y, Rosas R, Herbette G, Maigret B, Quelever G, Iwatsubo T, Kraus J. -L^*
    • Journal Title

      J Med Chem 49

      Pages: 4275-4285

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Synthesis of biotinylated photoaffinity probes based on arylsulfonamide γ-secretase inhibitors2006

    • Author(s)
      Fuwa H, Hiromoto K, Takahashi Y, Yokoshima S, Kan T, Fukuyama T, Iwatsubo T, Tomita T, Natsugari H^*
    • Journal Title

      Bioorg Med Chem Lett 16

      Pages: 4184-4189

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis2006

    • Author(s)
      Ozaki T, Li Y, Kikuchi H, Tomita T, Iwatsubo T, Nakagawara A^*
    • Journal Title

      Biochem Biophys Res Comm 351

      Pages: 57-63

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Structure of the catalytic pore of γ-secretase probed by the accessibility of substituted cysteines2006

    • Author(s)
      Sato C, Morohashi Y, Tomita T^*, Iwatsubo T^*
    • Journal Title

      J Neurosci 26

      Pages: 12081-12088

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Concise and short synthesis of functionalized 5, 6-Dihydropyridin-2-ones by means of palladium (0)-catalyzed cross-coupling of ketene aminal phosphates2006

    • Author(s)
      Fuwa H, Kaneko A, Sugimoto Y, Tomita T, Iwatsubo T, Sasaki M^*
    • Journal Title

      Heterocycles 70

      Pages: 101-106

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid β-peptide by the liver2006

    • Author(s)
      Tamaki C, Ohtsuki S, Iwatsubo T, Hashimoto T, Yamada K, Yabuki C, Terasaki T
    • Journal Title

      Pharmaceut Res 23

      Pages: 1407-1416

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Carboxy1-terminal fragment of presenilin is the molecular target of a dipeptidic γ -secretase-specific inhibitor DAPT.2006

    • Author(s)
      Morohashi Y
    • Journal Title

      J Biol Chem 281

      Pages: 14670-14676

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Novel γ -secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates.2006

    • Author(s)
      Takahashi Y
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters 16

      Pages: 3813-3816

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Presenilin-dependent intramembrane cleavage of ephrin-B 1.2006

    • Author(s)
      Tomita T
    • Journal Title

      Molecular Neurodegeneration 1

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Structure of the catalytic pore of γ -secretase inferred by the accessibility of substituted cysteines.2006

    • Author(s)
      Sato C
    • Journal Title

      J Neurosci 26

      Pages: 12081-12088

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Aph-1 contributes to the stabilization and trafficking of the y-secretase complex through mechanisms involving inter-and intramolecular interactions2005

    • Author(s)
      Niimura M
    • Journal Title

      J Biol Chem 280

      Pages: 12967-12975

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Association of active γ-secretase complex with lipid rafts2005

    • Author(s)
      Urano Y
    • Journal Title

      J Lipid Res 46

      Pages: 904-912

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Presenilin 2 regulates the systolic function of heart by modulating Ca2+ signaling2005

    • Author(s)
      Takeda T
    • Journal Title

      FASEB Journal 19

      Pages: 2069-2071

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Pen-2 is incorporated into the γ-secretase complex through binding to transmembrane domain 4 of presenilin 12005

    • Author(s)
      Watanabe N
    • Journal Title

      J Biol Chem 280

      Pages: 41967-41975

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] CLAC binds to amyloid β peptides through the positively-charged amino acid cluster within the collagenous domain 1 and inhibits formation of amyloid fibrils.2005

    • Author(s)
      Osada Y
    • Journal Title

      J Biol Chem 280

      Pages: 8596-8605

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2005 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aph-1 contributes to the stabilization and trafficking of the γ-secretase complex through mechanisms involving inter-and intramolecular interactions2005

    • Author(s)
      Niimura M, Isoo N, Takasugi N, Tsuruoka M, Ui-Tei K, Saigo K, Morohashi Y, Tomita T^*, Iwatsubo T^*
    • Journal Title

      J Biol Chem 280

      Pages: 12967-12975

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Association of active γ-secretase complex with lipid rafts2005

    • Author(s)
      Drano Y, Hayashi I, Isoo N, Reid PC, Shibasaki Y, Noguchi N, Tomita T, Iwatsubo T, Hamakubo T^*, Kodama T
    • Journal Title

      J Lipid Res 46

      Pages: 904-912

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Presenilin 2 regulates the systolic function of heart by modulating Ca2+ signaling2005

    • Author(s)
      Takeda T, Asahi M, Yamaguchi O, Hikoso S, Nakavama H, Kusakari Y, Kawai M, Hongo K, Higuchi Y, Kashiwase K, Watanabe T, Taniike M, Nakai A, Nishida K, Kurihara S, Donoviel DB, Bernstein A, Tomita T, Iwatsubo T, Hori M, Otsu K^*
    • Journal Title

      FASEB J. 19

      Pages: 2069-2071

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Pen-2 is incorporated into the γ-secretase complex through binding to transmembrane domain 4 of presenilin 12005

    • Author(s)
      Watanabe N, Tomita T^*, Sato C, Kitamura T, Morohashi Y, Iwatsubo T^*
    • Journal Title

      J Biol Chem 280

      Pages: 41967-41975

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] CLAC binds to amyloid β peptides through the positively-charged amino acid cluster within the collagenous domain 1 and inhibits formation of amyloid fibrils2005

    • Author(s)
      Osada Y, Hashimoto T, Nishimura A, Matsuo Y Wakabayashi T, Iwatsubo T.
    • Journal Title

      J Biol Chem 280

      Pages: 8596-8605

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Alph-1 contributes to the stabilization and trafficking of the γ-secretase complex through mechanisms involving inter- and intramolecular interactions.2005

    • Author(s)
      Niimura M
    • Journal Title

      J Biol Chem 280

      Pages: 12967-12975

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Pen-2 is incorporated into the γ-secretase complex through binding to transmembrane domain 4 of presenilin 1.2005

    • Author(s)
      Watanabe N
    • Journal Title

      J Biol Chem 280

      Pages: 41967-41975

    • Related Report
      2005 Annual Research Report
  • [Presentation] Structure and function of γ-secretase2008

    • Author(s)
      Iwatsubo T.
    • Organizer
      Keystone symposia, Alzheimer's disease
    • Place of Presentation
      Keystone
    • Year and Date
      2008-05-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] Alzheimer's disease:β-amyloid and γ-secretase2008

    • Author(s)
      Iwatsubo T.
    • Organizer
      10th Intemational Hong Kong/Springfield Symposium on Advances in Alzheimer Therapy
    • Place of Presentation
      Hong-Kong
    • Year and Date
      2008-05-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] Structure and function of γ-secretase2008

    • Author(s)
      Iwatsubo T
    • Organizer
      Keystone symposia
    • Place of Presentation
      Keystone
    • Year and Date
      2008-03-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Alzheimer's disease: β-amyloid and γ-secretase.2008

    • Author(s)
      Iwatsubo T
    • Organizer
      10th International Hong Kong/Springfield Symposium on Advances in Alzheimer Therapy
    • Place of Presentation
      Hong-Kong
    • Year and Date
      2008-03-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Alzheimer's disease : β-amyloid and γ-secretase2008

    • Author(s)
      Iwatsubo T
    • Organizer
      10th International Hong Kong/Springfield Symposium on Advances in Alzheimer Therapy
    • Place of Presentation
      Hong-Kong
    • Year and Date
      2008-03-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アルツハイマー病に対するJ-ADNI projectとバイオマーカー2008

    • Author(s)
      岩坪 威
    • Organizer
      第9回創薬ビジョンシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2008-01-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] ナノメディシンが拓く未来医療-ピンポイント診断・治療の実現を目指して-2007

    • Author(s)
      片岡 一則
    • Organizer
      第133回日本医学会シンポジウム「新しい技術がもたらす診断治療の可能
    • Place of Presentation
      日本医師会館大講堂
    • Year and Date
      2007-12-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] アルツハイマー病のdisease-modifing therapy:分子病態から臨床へ2007

    • Author(s)
      岩坪 威
    • Organizer
      第7回静岡ディメンシア懇話会
    • Place of Presentation
      浜松
    • Year and Date
      2007-11-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular pathology of Alzheimer's disease: β-amyloid and γ-secretase.2007

    • Author(s)
      Iwatsubo T
    • Organizer
      Japan-Korea Neuroscience Symposium
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-09-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular pathology of Alzheimer's disease : β-amyloid and γ-secretase2007

    • Author(s)
      Iwatsubo T
    • Organizer
      Japan-Korea Neuroscience Symposium
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-09-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular pathology of Alzheimer's disease2007

    • Author(s)
      Iwatsubo T.
    • Organizer
      β-amyloid and γ-secretase. Japan-Korea Neurosci ence Symposium "Cutting Edge of Neuroscience"
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-09-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] アルツハイマー病の分子病理学2007

    • Author(s)
      岩坪 威
    • Organizer
      Neuro 2007
    • Place of Presentation
      横浜
    • Year and Date
      2007-09-10
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular pathology of Alzheimer's disease: from benchside to clinics.2007

    • Author(s)
      Iwatsubo T
    • Organizer
      The 4th retreat of 21st century COE on brain medicine of the University of Tokyo
    • Place of Presentation
      Hakone
    • Year and Date
      2007-07-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular pathology of Alzheimer's disease : from benchside to clinics2007

    • Author(s)
      Iwatsubo T
    • Organizer
      The 4th retreat of 21st century COE on brain medicine of the University of Tokyo
    • Place of Presentation
      Hakone
    • Year and Date
      2007-07-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular pathology of Alzheimer's disease2007

    • Author(s)
      Iwatsubo T.
    • Organizer
      from benchside to clinics. The 4^〈th〉retreat of 21^〈st〉century COE on brain medicine of the University of Tokyo
    • Place of Presentation
      Hakone
    • Year and Date
      2007-07-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] アルツハイマー病の分子病理学2007

    • Author(s)
      岩坪 威
    • Organizer
      第48回日本神経病理学会総会学術研究会ランチョンセミナー
    • Place of Presentation
      東京
    • Year and Date
      2007-06-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] アルツハイマー病:基礎研究から根本治療へ2007

    • Author(s)
      岩坪 威
    • Organizer
      北海道大学大学院薬学研究院神経病理・病態生・化学(IBL)分野寄付講座開設記念シンポジウム「アルツハイマー病研究の100年と治療法・治療薬開発への道のり」
    • Place of Presentation
      札幌
    • Year and Date
      2007-05-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] γセクレターゼ・プレセニリンを標的とした治療戦略2007

    • Author(s)
      岩坪 威
    • Organizer
      第27回日本医学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular pathology of Alzheimer's disease: focusing on Aβ and γ-secretase.2007

    • Author(s)
      Iwatsubo T
    • Organizer
      Workshop on Alzheimer's disease and Parkinson's disease. RIKEN BSI
    • Place of Presentation
      Wako
    • Year and Date
      2007-03-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular pathology of Alzheimer's disease : focusing on Aβ and γ-secretase2007

    • Author(s)
      Iwatsubo T
    • Organizer
      Workshop on Alzheimer's disease and Parkinson's disease. RIKEN BSI
    • Place of Presentation
      Wako
    • Year and Date
      2007-03-15
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] γ-Secretase: Structure and Function.2006

    • Author(s)
      Iwatsubo T
    • Organizer
      Ringberg symposium on regulated membrane proteolysis
    • Place of Presentation
      Ringberg
    • Year and Date
      2006-11-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] γ-Secretase : Structure and Function2006

    • Author(s)
      Iwatsubo T
    • Organizer
      Ringberg symposium on regulated membrane Proteolysis
    • Place of Presentation
      Ringberg
    • Year and Date
      2006-11-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Alzheimer's disease: β-amyloid and γ-secretase as therapeutic targets.2006

    • Author(s)
      Iwatsubo T
    • Organizer
      The 4th COE international symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-11-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Alzheimer's disease : β-amyloid and γ-secretase as therapeutic targets2006

    • Author(s)
      Iwatsubo T
    • Organizer
      The 4th COE international symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-11-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Challenges for the enigma of Aβ and γ-secretase.2006

    • Author(s)
      Iwatsubo T
    • Organizer
      Alzheimer 100 years and beyond
    • Place of Presentation
      Tuebingen
    • Year and Date
      2006-11-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Challenges for the enigma of Aβ and γ-secretase2006

    • Author(s)
      Iwatsubo T
    • Organizer
      Alzheimer 100 years and beyond
    • Place of Presentation
      Tuebingen
    • Year and Date
      2006-11-04
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular pathology of Alzheimer's disease: β -amyloid and γ-secretase.2006

    • Author(s)
      Iwatsubo T
    • Organizer
      Wellcome Trust/CSHL Course Molecular Neurology and Neuropathology Lecture
    • Place of Presentation
      Cambridge
    • Year and Date
      2006-07-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] γ-Secretase.2006

    • Author(s)
      Iwatsubo T
    • Organizer
      Alzforum Tenth Anniversary Symposium. 10th International Meeting on Alzheimer's Disease and Related Disorders
    • Place of Presentation
      Madrid
    • Year and Date
      2006-07-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Structure and Function of presenilin. Demonstration of a water-accessible pore within γ-secretase by SCAM analysis.2006

    • Author(s)
      lwatsubo T
    • Organizer
      10th International Meeting on Alzheimer's Disease and Related Disorders
    • Place of Presentation
      Madrid
    • Year and Date
      2006-07-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Structure and Function of presenilin. Demonstration of a water-accessible pore within γ-secretase by SCAM analysis2006

    • Author(s)
      Iwatsubo T
    • Organizer
      10th International Meeting on Alzheimer's Disease and Related Disorders
    • Place of Presentation
      Madrid
    • Year and Date
      2006-07-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] g-Secretase2006

    • Author(s)
      Iwatsubo T
    • Organizer
      Alzforum Tenth Anniversary Symposium 10th International Meeting on Alzheimer's Disease and Related Disorders
    • Place of Presentation
      Madrid
    • Year and Date
      2006-07-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular pathology of Alzheimer's disease : β-amyloid and γ-secretase2006

    • Author(s)
      Iwatsubo T
    • Organizer
      Wellcome Trust/ CSHL Course Molecular Neurology and Neuropathology Lecture
    • Place of Presentation
      Cambridge
    • Year and Date
      2006-07-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Structure and Function of presenilin. Demonstration of a water-accessible pore within γ-secretase by SCAM analysis.2005

    • Author(s)
      Iwatsubo T
    • Organizer
      The 3rd Takeda Science Foundation Symposium on PharmaSciences: On the Frontiers of Neuro-PharmaSciences-Molecular Pathology and Drug Action
    • Place of Presentation
      Tokyo
    • Year and Date
      2005-12-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Molecular Pathology of Alzheimer's disease : β-amyloid and γ-secretase2005

    • Author(s)
      Iwatsubo T
    • Organizer
      The 3rd Takeda Science Foundation Symposium on PharmaSciences : On the Frontiers of Neuro-PharmaScie-Molecular Pathology and DrugAction
    • Place of Presentation
      Tokyo
    • Year and Date
      2005-12-05
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Structure and function of γ-secretase.

    • Author(s)
      Iwatsubo T
    • Organizer
      Keystone symposia, Alzheimer's disease
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.f.u-tokyo.ac.jp/~neuropsc/index.html

    • Related Report
      2007 Final Research Report Summary

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi