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Development of novel diagnostic and therapeutic methods on Alzheimer's disease by targeting amyloid oligomers

Research Project

Project/Area Number 26290022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionShiga University of Medical Science

Principal Investigator

Tooyama Ikuo  滋賀医科大学, 神経難病研究センター, 教授 (20207533)

Co-Investigator(Kenkyū-buntansha) 椎野 顯彦  滋賀医科大学, 神経難病研究センター, 准教授 (50215935)
田口 弘康  滋賀医科大学, 神経難病研究センター, 特任教授 (90102912)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywords脳神経疾患 / アルツハイマー病 / 核磁気共鳴画像 / 診断 / 治療 / アミロイドオリゴマー / ベータアミロイド / タウタンパク / オリゴマー / 神経科学 / 認知症 / 神経化学 / 老化
Outline of Final Research Achievements

The aim of this study is to find curcumin derivatives that have diagnostic and therapeutic potential for Alzheimer's disease (AD). We used, f-methyl-curcumin1 (FMeC1) and FMeC2. For MRI, FMeC1 or FMeC2 (200 mg/kg) was injected into the tail vein of six Tg2576, three APP/PS1 and six control mice. Then, amyloid imaging was employed using a 7.0 T MR scanner. For therapeutic experiments, 36 model mice and 12 wild mice were divided into four groups; control diet, curcumin, FMeC1 or FMeC2 group. FMeC1, or FMeC2 (500 ppm) for 6 months from 9-month-old. Behavioral tests were conducted from 14.5 months of age, and mice were sacrificed at 15 months of age for pathological analyses. FMeC1 but not FMeC2 successfully detected amyloid plaques in living mice. Only FMeC1 showed a significant improvement on cognitive function compared to control group (p < 0.05). In addition, FMeC1 reduced Aβ aggregation and glial cell activity (p < 0.05). FMeC1 is a potential diagnostic and therapeutic agent for AD.

Report

(4 results)
  • 2017 Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (30 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (3 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 8 results,  Acknowledgement Compliant: 7 results) Presentation (14 results) (of which Int'l Joint Research: 8 results,  Invited: 3 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] ハルピン医科大学(中国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] マレーシア国民大学(マレーシア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] マレーシア国民大学(マレーシア)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Tocotrienol-rich fraction modulates amyloid pathology and improves cognitive function in AβPP/PS1 mice.2017

    • Author(s)
      Ibrahim NF, Yanagisawa D, Durania LW, Hamezaha HS, HDamanhuri HD, Wan Ngahb WZ, Tsuji M, Kiuchi Y, Ono K, Tooyama I
    • Journal Title

      Journal of Alzheiemrs Disease

      Volume: 55 Issue: 2 Pages: 597-617

    • DOI

      10.3233/jad-160685

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Sex-related difference in human white matter volumes studied: Inspection of the corpus callosum and other white matter by VBM.2017

    • Author(s)
      Shiino A, Chen Y-W, Tanigaki K, Yamada A, Vigers P, Watanabe T, Tooyama I, Akiguchi I
    • Journal Title

      Scientific Reports

      Volume: 3 Pages: 39818-39818

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fluorodopa is a promising fluorine-19 MRI probe for evaluating striatal dopaminergic function in a rat model of Parkinson’s disease.2017

    • Author(s)
      Yanagisawa D, Oda K, Inden M, Morikawa S, Inubushi T, Taniguchi T, Hijioka M, Kitamura Y, Tooyama I
    • Journal Title

      Journal of Neuroscience Research

      Volume: 印刷中 Issue: 7 Pages: 1485-1494

    • DOI

      10.1002/jnr.23983

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Amyloid imaging using fluorine-19 magnetic resonance imaging (19F-MRI).2016

    • Author(s)
      Tooyama I, Yanagisawa D, Taguchi H, Kato T, Hirao K, Shirai N, Sogabe T, Ibrahim NF, Inubushi T, Morikawa S
    • Journal Title

      Ageing Research Reviews

      Volume: 15 Pages: 1568-1637

    • DOI

      10.1016/j.arr.2015.12.008

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mapping of mitochondrial ferritin in the brainstem of Macaca fascicularis.2016

    • Author(s)
      Yang M, Yang H, Guan H, Bellier JP, Zhao S, Tooyama I
    • Journal Title

      Neuroscience

      Volume: 328 Pages: 92-106

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Novel curcumin derivatives as potent inhibitors of amyloid β aggregation.2015

    • Author(s)
      Yanagisawa D, Taguchi H, Morikawa S, Kato T, Hirao K, Shirai N, Tooyama I
    • Journal Title

      Biochem Biophys Report

      Volume: 4 Pages: 357-368

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis and Tautomerism of Curcumin Derivatives and Related Compounds.2015

    • Author(s)
      Taguchi H, Yanagisawa D, Morikawa S, Hirao K, Shirai N, Tooyama I
    • Journal Title

      Australian Journal of Chemistry

      Volume: 68 Pages: 224-229

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Up-regulation of mitochondrial ferritin by proinflammatory cytokines: Implications for a role in Alzheimer’s disease.2015

    • Author(s)
      Yang H, Guan H, Yang M, Liu Z, Takeuchi S, Yanagisawa D, Vincent SR, Zhao S, Tooyama I
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 45 Issue: 3 Pages: 797-811

    • DOI

      10.3233/jad-142595

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Alpha1-chimaerin, a Rac1 GTPase-activating protein, is expressed at reduced mRNA levels in the brain of Alzheimer's disease patients.2015

    • Author(s)
      Kato T, Konishi Y, Shimohama S, Beach TG, Akatsu H, Tooyama I
    • Journal Title

      Neurosci Lett.

      Volume: 5901 Pages: 19-24

    • DOI

      10.1016/j.neulet.2015.02.013

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhalable Curcumin: Offering the Potential for Translation to Imaging and Treatment of Alzheimer's Disease.2014

    • Author(s)
      McClure R, Yanagisawa D, Stec D, Koktysh D, Xhillari D, Jaeger R, Chekmenev E, Tooyama I, Gore1 JC, Pham W
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 144 Issue: 1 Pages: 283-295

    • DOI

      10.3233/jad-140798

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Curcumin derivative with substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PSI mice2014

    • Author(s)
      Yanagisawa D, Ibraham NF, Taguchi H, Morikawa S, Hirao K, Shirai N, Sogabe T, Tooyama I
    • Journal Title

      Neurobiol Aging

      Volume: 36 Issue: 1 Pages: 210-210

    • DOI

      10.1016/j.neurobiolaging.2014.07.041

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] A novel curcumin derivative, f-methyl-curcumin-1 (fmec1), is a potential diagnostic and therapeutic agent for Alzheimer's disease.2016

    • Author(s)
      Tooyama, D. Yanagisawa, N. F. Ibrahim, H. Taguchi
    • Organizer
      14th Meeting of Asia-Pacific Society for Neurochemistry
    • Place of Presentation
      クアラルンプール、マレーシア
    • Year and Date
      2016-07-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] pplication of double MR imaging to detect amyloid oligomers in the brain of APP/PS1 transgenic model mice.2016

    • Author(s)
      Ikuo Tooyama, Daijiro Yanagisawa, Hiroyasu Taguchi, Tomoko Kato, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Shigehiro Morikawa
    • Organizer
      Alzheimer's Association International Conference 2016
    • Place of Presentation
      トロント、カナダ
    • Year and Date
      2016-07-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] フッ素MR画像化法によるAβオリゴマーの検出の開発2016

    • Author(s)
      柳沢大治郎、Nor Faeizah Ibrahim、田口弘康、森川茂廣、遠山育夫:
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development on Shiga-Y, a potential diagnostic and therapeutic agent for Alzheimer's disease, using mouse model of dementia2016

    • Author(s)
      Ikuo Tooyama, Daijiro Yanagisawa, Tomoko, Kato, Nor Faeizah Ibrahim, Lina Wati Durani, Hamizah Shahirah Hamezah, Hiroyasu Taguchi
    • Organizer
      第31回SAMサテライト国際シンポシウム
    • Place of Presentation
      京都
    • Year and Date
      2016-07-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アルツハイマー病の病態解明のためのフッ素MRIによるダブルプローブイメージング法の開発2016

    • Author(s)
      柳沢大治郎、Nor Faeizah Ibrahim、田口弘康、森川茂廣、遠山育夫
    • Organizer
      第11回日本分子イメージング学会
    • Place of Presentation
      神戸
    • Year and Date
      2016-05-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] -methyl-curcumin-1 is a potential diagnostic and therapeutic agent for Alzheimer's disease.2016

    • Author(s)
      Ikuo Tooyama, Daijiro Yanagisawa, Hiroyasu Taguchi, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Tomoko Kato, Shieghiro Morikawa
    • Organizer
      第57回日本神経学会総
    • Place of Presentation
      神戸
    • Year and Date
      2016-05-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] Styrylbenzoxazole and curcumin derivatives that have preferred features of a fluorine-19 MRI probe for amyloid imaging.2015

    • Author(s)
      Ikuo Tooyama, Daijiro Yanagisawa, Hiroyasu Taguchi, Nor Faeizah Ibrahim, Lina Wati Durani, Hamizah Shahirah Hamezah, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Shigehiro Morikawa
    • Organizer
      国際分子イメージング学会2015
    • Place of Presentation
      米国ホノルル市
    • Year and Date
      2015-09-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of novel curcumin derivatives on amyloid aggregation and the cell toxicity2015

    • Author(s)
      柳沢大治郎、Nor Faeizah Ibrahim、Lina Wati Durani、Hamizah Shahirah Hamezah、田口弘康、遠山育夫
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of Novel Curcumin Derivative with C-4 Substituent on Cognitive Impairment and Amyloid Deposition in Appswe/PS1dE9 Mice.2015

    • Author(s)
      Daijiro Yanagisawa, Nor Faeizah Ibrahim, Lina Wati Durani, Hamizah Shahirah Hamezah, Hiroyasu Taguchi, Shigehiro Morikawa, Koichi Hirao, Nobuaki Shirai, and Ikuo Tooyama
    • Organizer
      アルツハイマー協会国際会議(AAIC)2015
    • Place of Presentation
      米国ワシントンDC
    • Year and Date
      2015-07-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] argeting Antioxidant Pathways in Neurodegeneration2015

    • Author(s)
      Ikuo Tooyama:
    • Organizer
      第1回抗酸化物質sと細胞変性に関する国際会議
    • Place of Presentation
      マレーシア国クアラルンプール市
    • Year and Date
      2015-06-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] フッ素MRIを利用したAβオリゴマーの画像化法の開発2015

    • Author(s)
      柳沢大治郎、Nor Faeizah Ibrahim、田口弘康、森川茂廣、遠山育夫
    • Organizer
      第10回日本分子イメージング学会総会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel curcumin derivative with C-4 substituent inhibits amyloid pathology in APPswe/PS1dE9 mice2014

    • Author(s)
      Yanagisawa D, Taguchi H, Ibrahim NF, Durani L, Morikawa S, Hirao K, Shirai N, Sogabe T, Tooyama I
    • Organizer
      北米神経科学会議(Neuro2014)
    • Place of Presentation
      ワシントンDC、米国
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] クルクミン誘導体によるAβ凝集抑制効果とAβによる細胞障害軽減効果の解析2014

    • Author(s)
      柳沢大治郎、遠山育夫、Ibrahim, Nor Faeizah、田口弘康
    • Organizer
      第11回サプリメント研究会
    • Place of Presentation
      東京、日本
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effect of novel curcumin derivatives on amyloid pathology in APP/PS1 mice2014

    • Author(s)
      Daijiro Yanagisawa, Nor Faeizah Ibrahim, Lina Wati Durani, Hiroyasu Taguchi, Ikuo Tooyama
    • Organizer
      第37回日本神経科学学会学術大会
    • Place of Presentation
      横浜市、日本
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Book] FRUITS, VEGETABLES AND HERBS: Bioactive Foods in Health Promotion2016

    • Author(s)
      Tooyama I, Ibrahim NF, Durani LW, Haemzah HS, Damanhuri MHA, Wan Ngah WZ, Taguchi H, Yanagisawa D
    • Total Pages
      593
    • Publisher
      Elsevier
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 神経難病の画像診断薬及び体外診断薬2017

    • Inventor(s)
      遠山育夫, 田口弘康、柳沢大治郎、曾我部孝行、白井伸明、平尾浩一
    • Industrial Property Rights Holder
      滋賀医科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-046350
    • Filing Date
      2017-03-10
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2022-02-16  

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