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Protective mechanism of neuronal system by heat shock transcription factor 2

Research Project

Project/Area Number 17K07136
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory animal science
Research InstitutionYamaguchi University

Principal Investigator

HAYASHIDA Naoki  山口大学, 大学院医学系研究科, 講師 (40420517)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsHSF2 / HSF1 / ヒト神経細胞 / 変異型タウタンパク質 / ベータアミロイド / 神経変性疾患 / 軸索 / 凝集体 / 神経細胞 / SH-SY5Y / Neuro-2a / 熱耐性 / タウ / アルツハイマー病 / アルツハイマー病モデルマウス / 転写 / 脳神経疾患 / 老化 / 細胞・組織 / 痴呆 / 発現制御
Outline of Final Research Achievements

While we investigate the protective mechanism of neuronal system by heat shock transcription factor 2 (HSF2), we found some chemical compounds and peptides that can be drug candidate for neurodegenerative diseases (NDDs) and dementia. Especially, phorbol ester PMA and one glycan species. Intracellular aggregate formation and axonal degeneration and/or inhibition of axonal growth is characteristic pathological phenomenon of NDDs, but our two drugs dramatically improve these pathology. Moreover, we also discovered that HSF2 has an essential roles in both drugs' effects. Finally, not only our purpose of this grant-in-aid has well achieved but also we could discover the strong candidate chemicals for the development of therapeutic drugs for NDDs.

Academic Significance and Societal Importance of the Research Achievements

学術的には、脳神経系保護においてHSF2が大きく関わっていることを示せたほか、これまでのHSFの知見では考えられなかった新たなメカニズムを見出すことが出来たことは意義が大きい。一方、本研究において、これまで世界中の製薬会社や大学、公的研究機関が開発研究を実施しながら1つも成功していない「神経変性疾患(NDDs)の治療薬」の新たなシーズとなりうる物質群を発見できたこと、さらにその2つにおいては、強力な効果が確認出来たことが、社会的意義としては非常に大きい。この2つの物質は、NDDsの重篤な症状である認知症状を回復出来る可能性があるだけでなく、うち1つは毒性が非常に低いことも特筆すべき点であった。

Report

(3 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results)

  • [Journal Article] Structures of the antibody 64M-5 Fab and its complex with dT(6-4)T indicate induced-fit and high-affinity mechanisms.2019

    • Author(s)
      Yokoyama H, Mizutani R, Noguchi S, Hayashida N.
    • Journal Title

      Acta Crystallogr F Struct Biol Commun

      Volume: 75(Pt 2) Issue: 2 Pages: 80-88

    • DOI

      10.1107/s2053230x18017661

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Phorbol Ester Inhibits Inclusion Formation and Accelerates Neurite Growth in Neuronal Cells2018

    • Author(s)
      Yasuko TOKUNAGA, Masami MOMONAKA, Kaoru HAYASHIDA, Naoki HAYASHIDA
    • Organizer
      第41回日本基礎老化学会総会(東京)
    • Related Report
      2017 Research-status Report
  • [Presentation] Identification of Small Compounds Protecting Neuronal Cells from the Toxicity of Proteins that Cause Neurodegenerative Diseases2017

    • Author(s)
      Masami Mononaka, Yasuko Tokunaga, Naoki Hayashida
    • Organizer
      第40回日本基礎老化学会総会(名古屋)
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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