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Control of lipid metabolism by a novel autophagic system for the prevention of neurodegenerative disorders

Research Project

Project/Area Number 17K07124
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Wada Keiji  国立研究開発法人国立精神・神経医療研究センター, 神経研究所, 所長 (70250222)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords脳・神経 / 脂質 / オートファジー / マウス / リソソーム / 脂質代謝 / 予防
Outline of Final Research Achievements

In this study, we investigated whether synaptic instability due to maternal lipid loading affects postnatal morbidity and whether the novel autophagy system we found was involved. The social behavioral evaluation using the three-chamber test and the contextual fear conditioning evaluation were used, but no significant difference was found between the control offspring and the offspring from the maternal mouse with high-fat diet intake during lactation. Besides, we have constructed genetically engineered mice for the constituent molecules of the new autophagy system and are currently analyzing the effects of lipid loading.

Academic Significance and Societal Importance of the Research Achievements

現在の創薬は「脳の中」に発現する分子を薬剤開発の標的とすることがほとんどである。しかしなかなか良い治療薬が生まれていないのも事実である。我々が行う脳・臓器間ネットワーク研究は「脳の外」に標的を求めるという新たな発想を提示することになる。昨今流行のバイオマーカー探索についても何をもってバイオマーカーとするかという根本的なところから課題を提出し、解を示す。脳・臓器間ネットワークの概念の浸透は薬効評価型のバイオマーカー開発についても、「脳の外」で最初期から変動するバイオマーカーを探索する必要性を確立することになる。従来型の治療薬開発が功を奏しないなかで、本研究は新たな可能性を提示する。

Report

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

    (3 results)

All 2020 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Journal Article] Participation of the nucleus accumbens dopaminergic system in the antidepressant-like actions of a diet rich in omega-3 polyunsaturated fatty acids2020

    • Author(s)
      Takeuchi Eri、Yamada Daisuke、Suzuki Satoshi、Saitoh Akiyoshi、Itoh Masayuki、Hayashi Takashi、Yamada Mitsuhiko、Wada Keiji、Sekiguchi Masayuki
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 3 Pages: e0230647-e0230647

    • DOI

      10.1371/journal.pone.0230647

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cytosolic domain of SIDT2 carries an arginine-rich motif that binds to RNA/DNA and is important for the direct transport of nucleic acids into lysosomes2020

    • Author(s)
      Hase Katsunori、Contu Viorica Raluca、Kabuta Chihana、Sakai Ryohei、Takahashi Masayuki、Kataoka Naoyuki、Hakuno Fumihiko、Takahashi Shin-Ichiro、Fujiwara Yuuki、Wada Keiji、Kabuta Tomohiro
    • Journal Title

      Autophagy

      Volume: NO Issue: 11 Pages: 1-15

    • DOI

      10.1080/15548627.2020.1712109

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathological role of lipid interactions with α-synuclein in Parkinson’s disease.2018

    • Author(s)
      271.Suzuki, M., Wada, K., Sango, K., Nagai, Y
    • Journal Title

      Neurochem Int

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed

URL: 

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

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