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Screening of novel therapeutic molecules against neurodegenerative diseases via modulation of Hdac activity

Research Project

Project/Area Number 24500972
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Eating habits, studies on eating habits
Research InstitutionUniversity of Yamanashi

Principal Investigator

NAGAI Kaoru  山梨大学, 総合研究部, 准教授 (20340953)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords機能性食品 / ヒストン脱アセチル化酵素 / 認知症予防 / 健康と食生活 / 神経変性疾患予防
Outline of Final Research Achievements

By screening of Hdac inhibitory molecules, we found that Brazilian propolis extract (BPE) showed Hdac inhibitory effect. BPE also protected neuronal cells from endoplasmic reticulum stress induced cell death, which causes most of the neurodegenerative diseases.
We studied the Hdac modulating effects of branched fatty acid phytanic acid (PA), which is a metabolic intermediate of chlorophyll in beef and dairy products. Although generally fatty acids were reported to show Hdac inhibitory effects, PA showed Hadc activating effect. And PA induced neuronal cell death. During this study, we found that Hdac modulation associated with mitochondrial activity in neuronal cells. Our data suggests that the mitochondrial activations might be involved in the neuroprotective functions of Hdac inhibitory molecules.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (13 results)

  • [Journal Article] Phytanic acid induces Neuro2a cell death via histone deacetylase activation and mitochondrial dysfunction.2015

    • Author(s)
      Nagai K
    • Journal Title

      Neurotoxicology and Teratology

      Volume: 48 Pages: 33-39

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Histone deacetylase inhibitory effect of Brazilian propolis and its association with the anti-tumor effect in Neuro2a cells.2014

    • Author(s)
      Ishiai S, Tahara W, Yamamoto E, Yamamoto R, Nagai K.
    • Journal Title

      Food Science & Nutrition

      Volume: 2 Issue: 5 Pages: 565-570

    • DOI

      10.1002/fsn3.131

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Histone deacetylase inhibitory effect of Brazilian propolis and its association with the anti-tumor effect in Neuro2a cells.2014

    • Author(s)
      Ishiai S, Tahara W, Yamamoto E, Yamamoto R, Nagai K
    • Journal Title

      Food Sci. Nutr.

      Volume: 2

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Phytanic acid induces Neuro2a cell death via histone deacetylase activation.2014

    • Author(s)
      Nagai K
    • Organizer
      Annual Meeting of Society for Neuroscience
    • Place of Presentation
      Washington DC (USA)
    • Year and Date
      2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] フィタン酸はヒストン脱アセチル化酵素(Hdac)活性化とミトコンドリア障害を介しNeuro2a細胞に細胞死を誘導する2014

    • Author(s)
      長井 薫, 名取 貴光
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] アントシアニンのヒストン脱アセチル化を介した神経細胞保護および神経突起伸長作用2014

    • Author(s)
      名取 貴光, 長井 薫
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] ブラジル産プロポリス抽出物による小胞体ストレスからのNeuro2a細胞保護効果2013

    • Author(s)
      石合 忍, 田原 渉, 山本 悦子, 山本 倫大, 長井 薫
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県)
    • Related Report
      2012 Research-status Report
  • [Presentation] フィタン酸によるヒストン脱アセチル化酵素活性化作用2013

    • Author(s)
      長井 薫
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県)
    • Related Report
      2012 Research-status Report
  • [Presentation] ブラジル産プロポリスによるヒストン脱アセチル化酵素活性制御と神経保護作用2012

    • Author(s)
      石合 忍, 田原 渉, 山本 倫大, 長井 薫
    • Organizer
      第35回日本神経科学会大会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Research-status Report
  • [Presentation] Neuroprotective effect of Brazilian propolis extract via regulating Hdac activities.2012

    • Author(s)
      Ishiai S, Tahara W, Yamamoto R, Nagai K.
    • Organizer
      Annual Meeting of Society for Neuroscience
    • Place of Presentation
      Ernest N. Memorial Convention Center (New Orleans, USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] フィタン酸はヒストン脱アセチル化酵素を活性化しNeuro2a細胞への小胞体ストレスを強める

    • Author(s)
      長井 薫
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Relationship of histone deacetylation and natural product-derived pigments exhibit anti-inflammatory activity and neuroprotective effects

    • Author(s)
      名取 貴光, 長井 薫
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Phytanic acid enhances histone deacetylase activity and vulnerability to endoplasmic reticulum stress in Neuro2a cells.

    • Author(s)
      Nagai K
    • Organizer
      Annual Meeting of Society for Neuroscience
    • Place of Presentation
      San Diego Convention Center (San Diego, USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] Protective effect of Brazilian propolis and its major component Artepillin C on endoplasmic reticulum stress induced Neuro2a cell death.

    • Author(s)
      Ishiai S, Tahara W, Yamamoto R, Nagai K
    • Organizer
      Annual Meeting of Society for Neuroscience
    • Place of Presentation
      San Diego Convention Center (San Diego, USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] フィタン酸によるヒストン脱アセチル化酵素活性化を介したNeuro2a細胞に対する毒性作用

    • Author(s)
      長井 薫
    • Organizer
      日本農芸化学会2014年度大会
    • Place of Presentation
      明治大学生田キャンパス (神奈川県川崎市)
    • Related Report
      2013 Research-status Report
  • [Presentation] ポリフェノール類によるヒストン脱アセチル化酵素(Hdac)活性制御と神経機能調節

    • Author(s)
      名取 貴光, 長井 薫
    • Organizer
      日本農芸化学会2014年度大会
    • Place of Presentation
      明治大学生田キャンパス (神奈川県川崎市)
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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