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Development of Imaging technique for Alzheimer's disease

Research Project

Project/Area Number 19689002
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionKyushu University

Principal Investigator

YAMADA Kenichi  Kyushu University, 大学院・薬学研究院, 准教授 (60346806)

Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
Fiscal Year 2009: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2008: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2007: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Keywordsアミロイド / フリーラジカル / 磁気共鳴 / ニトロキシルラジカル
Research Abstract

Alzheimer's disease is most common neurodegenerative disorder, which is characterized by progressive memory deficit, cognitive impairment and personal changes. The main pathogenesis is thought extracellular deposits of a short peptide referred to as amyloid β (Aβ), which is major component of the plaque. However, the molecular mechanism for Aβ aggregation process is not well defined. Herein, the aim of this study was to develop new Aβ binding nitroxide to detect fibrils and understand an aggregation process. Aβ binding nitroxide was designed from 6-methoxybenzothiazoleaniline. Fluorescence and ESR spectroscopic analysis demonstrated that the nitroxide banded to Aβ fibrils. Further, we succeeded in detecting of fibrillization process by analyzing the change of ESR spectrum. Another advantage of Aβ binding nitroxide was an antioxidant effect. These findings indicated that new nitroxide can detect Aβ fibrils and evaluate an aggregation process with ESR spectroscopy.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (25 results)

All 2010 2009 2008 2007

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (6 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Effective 2, 6-substitution of piperidine nitroxyl radical by carbonyl compound.2010

    • Author(s)
      Sakai, K., Yamada, K., Yamasaki, T., Kinoshita, Y., Mito, F., Utsumi, H.
    • Journal Title

      Tetrahedron 66

      Pages: 2311-2315

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic nuclear polarization studies of redox-sensitive nitroxyl spin probes in liposomal solution.2010

    • Author(s)
      Benial, AM., Utsumi, H., Ichikawa, K., Murugesan, R., Yamada, K., Kinoshita, Y., Naganuma, T., Kato, M.
    • Journal Title

      J. Magn. Reson. 204(1)

      Pages: 131-8

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Determination of reactive oxygen species associated with the degeneration of dopaminergic neurons during dopamine metabolism.2010

    • Author(s)
      Yamato M, Kudo W, Shiba T, Yamada KI, Watanabe T, Utsumi H.
    • Journal Title

      Free Radic. Res. 44(3)

      Pages: 249-57

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effective 2,6-substitution of nitroxyl radical by carbonyl compound2010

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

      Tetrahedon 66

      Pages: 2311-2315

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic nuclear polarization studies of redox-sensitive nitroxyl spin probes in liposomal solution2010

    • Author(s)
      Benial AM, et al.
    • Journal Title

      J Magn Reson 204

      Pages: 131-138

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Noninvasive assessment of the brain redox status after transient middle cerebral artery occlusion using Overhauser-enhanced magnetic resonance imaging.2009

    • Author(s)
      amato, M., Shiba, T., Yamada, K,, Watanabe, T., Utsumi, H
    • Journal Title

      J. Cereb. Blood Flow Metab. 29(10)

      Pages: 1655-1664

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of novel nitroxyl radicals for controlling reactivity with ascorbic acid.2009

    • Author(s)
      Kinoshita, Y., Yamada, K., Yamasaki, T., Sadasue, H., Sakai, K., Utsumi, H.
    • Journal Title

      Free Radic. Res. 43

      Pages: 565-571

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Separable detection of lipophilic- and hydrophilicphase free radicals from the ESR spectrum of nitroxyl radical in transient MCAO mice.2009

    • Author(s)
      Yamato, M., Shiba, T., Yamada, K., Watanabe, T., Utsumi, H.
    • Journal Title

      Free Radic. Res. 43

      Pages: 844-851

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Noninvasive assessment of the brain redox status after transient middle cerebral artery occlusion using Overhauser-enhanced magnetic resonance imaging2009

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

      J Cereb Blood Flow Metab 29

      Pages: 1655-1664

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determination of reactive oxygen species associated with the degeneration of dopaminergic neurons during dopamine metabolism.2009

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

      Free Radic Res 44

      Pages: 1249-257

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of novel nitroxyl radicals for controlling reactivity with ascorhic acid2009

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

      Free Radic Res (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of nitroxyl radicals for Overhauser-enhanced magnetic resonance imaging.2008

    • Author(s)
      Yamada, K., Kinoshita, Y., Yamasaki, T., Sadasue, H., Mito, F., Nagai, M., Matsumoto, S., Aso, M., Suemune, H., Sakai, K., Utsumi, H
    • Journal Title

      Arch. Pharm. 341

      Pages: 548-553

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Formation of TEMPOL-hydroxylamine during reaction between TEMPOL and hydroxyl radical: HPLC/ECD study.2008

    • Author(s)
      Kudo, W., Yamato, M., Yamada, K., Kinoshita, Y., Shiba, T., Watanabe, T., Utsumi, H.
    • Journal Title

      Free Radic. Res. 42

      Pages: 505-512

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of nitroxyl spin probes in mouse brain by X-band ESR with microdialysis technique2008

    • Author(s)
      Shiba, T., Yamato, M., Kudou, W., Ichikawa, K., Yamada, K., Watanabe, T., Utsumi, H.
    • Journal Title

      J. Pharm. Sci. 97

      Pages: 4101-4107

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of nitroxyl radicals for Overhauser-enhanced magnetic resonance imaging2008

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

      Arch Pharm (Weinheim) 341

      Pages: 548-553

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation of TEMPOL-hydroxylamine during reaction between TEMPOL and hydroxyl radical : HPLC/ECD study2008

    • Author(s)
      Kudo W, et.al.
    • Journal Title

      Free Radic Res 42

      Pages: 505-512

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of nitroxyl spin probes in mouse brain by X-band ESR with microdialysis technique2008

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

      J Pharm Sci (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Synthesis of 2, 6-disubstituted and 15N-labeled TEMPO Derivatives.2008

    • Author(s)
      Yamada, K., Sakai, K., Utsumi, H
    • Organizer
      EPR2008: A Joint Conference of 13th In Vivo EPR Spectroscopy and Imaging 10th International EPR Spin Trapping/Spin Labeling.
    • Place of Presentation
      Fukuoka
    • Related Report
      2009 Final Research Report
  • [Presentation] Stability Evaluation for 2, 6-substituted TEMPO Derivatives in the Reduction Process.2008

    • Author(s)
      Kinoshita, Y., Yamada, K., Sadasue, H., Yamasaki, T., Sakai, K., Utsumi, H.
    • Organizer
      SPIN 2008: 5th International Conference on Nitroxide Radicals.
    • Place of Presentation
      Ancona, Italy
    • Related Report
      2009 Final Research Report
  • [Presentation] 生体内フリーラジカル反応の可視化に向けた新規ニトロキシルラジカルの開発2008

    • Author(s)
      山田健一
    • Organizer
      第61日本酸化ストレス学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] オーバーハウザー効果mr iを用いた生体内レドックス変動の画像解析2008

    • Author(s)
      山田健一
    • Organizer
      ナノictシンポジウム、nano tech 2008
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Presentation] Synthesis and Evaluation of Novel Nitroxyl Radicals binding to amyloid beta protein.2007

    • Author(s)
      Sadasue, H., Yamasaki, T., Yamada, K., Sakai, K., Utsumi, H
    • Organizer
      The 4th JSPS core-to core Program Seminar International In Vivo Redox Symposium.
    • Place of Presentation
      Shizuoka.
    • Related Report
      2009 Final Research Report
  • [Presentation] オーバーハウザー効果MRIによる生体内レドックスの可視化2007

    • Author(s)
      山田健一
    • Organizer
      第7回日本抗加齢医学会総会、「先端技術を応用した活性酸素研究の現状と将来」シンポジスト
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] ニトロキシルラジカルの合成法2008

    • Inventor(s)
      内英雄、酒井淨、山田健一
    • Industrial Property Rights Holder
      国立大学法人九州大学
    • Filing Date
      2008-01-30
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] ニトロキシルラジカルの合成法2008

    • Inventor(s)
      内海英雄、酒井浄、山田健一
    • Industrial Property Rights Holder
      内海英雄、酒井浄、山田健一
    • Filing Date
      2008-01-30
    • Related Report
      2007 Annual Research Report
    • Overseas

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

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