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Understanding the Molecular Mechanisms of Lipid Metabolism Disruption-induced Age-Related Neurodegeneration

Research Project

Project/Area Number 18K14835
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionNiigata University

Principal Investigator

Nitta Yohei  新潟大学, 脳研究所, 特任助教 (30800429)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsショウジョウバエ / 脂質代謝 / 神経変性 / 神経発生 / キノコ体 / CDP-DAG / PIP2
Outline of Final Research Achievements

In this study, I have attempted to elucidate the molecular mechanism by which neurons degenerate from axon terminals in an age-dependent manner caused by disorder of lipid metabolism. I found that the neurodegeneration is triggered by the induction of disturbances in phospholipid metabolism immediately following the differentiation of neurons. Interestingly, the onset of neurodegeneration is not immediate; elongation and projection are normal. It is possible that the disturbance of the phospholipid metabolism affects the morphological maintenance mechanism of the neuron. By genetic analysis, we identified that this degeneration was caused by a decrease in phosphatidylinositol 4,5-bisphosphate (PI (4,5) P2). PI3K and PLC, the major metabolic enzymes of PI (4,5) P2, are not involved, suggesting that an unknown molecular mechanism may control this degeneration.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、分化直後の神経細胞が頑健性を獲得するのにリン脂質の代謝が必須なことが明らかとなった。この現象は細胞膜に局在するリン脂質の1つであるPI(4,5)P2が関与している。興味深いことに神経細胞の発生が完了した後にPI(4,5)P2を減少させても変性が観察されなかったことから、PI(4,5)P2依存的かつ時期特異的な神経細胞の頑健性獲得メカニズムの存在を強く示唆している。神経変性疾患においても、神経細胞のリン脂質の組成が異常になることが知られており、本研究によって提供される知見によって神経細胞変性の抑制が期待できる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 7 results) Presentation (6 results) Remarks (2 results)

  • [Int'l Joint Research] DZNE(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] A quantitative model of sporadic axonal degeneration in the Drosophila visual system2022

    • Author(s)
      Melisande Richard, Karolina Doubkova, Yohei Nitta, Hiroki Kawai, Atsushi Sugie, Gaia Tavosanis
    • Journal Title

      The Journal of Neuroscience

      Volume: - Issue: 24 Pages: 4937-4952

    • DOI

      10.1523/jneurosci.2115-21.2022

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <i>De novo ARF3</i> variants cause neurodevelopmental disorder with brain abnormality2021

    • Author(s)
      Sakamoto M、Sasaki K、Sugie A、Nitta Y、Kimura T、G?rsoy S、Cinleti T、Iai M、Sengoku T、Ogata K、Suzuki A、Okamoto N、Iwama K、Tsuchida N、Uchiyama Y、Koshimizu E、Fujita A、Hamanaka K、Miyatake S、Mizuguchi T、Taguri M、Ito S、Takahashi H、Miyake N、Matsumoto N
    • Journal Title

      Human Molecular Genetics

      Volume: 31 Issue: 1 Pages: 69-81

    • DOI

      10.1093/hmg/ddab224

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MeDUsA: A novel system for automated axon quantification to evaluate neuroaxonal degeneration2021

    • Author(s)
      Nitta Yohei、Kawai Hiroki、Osaka Jiro、Hakeda-Suzuki Satoko、Nagai Yoshitaka、Doubkov? Karol?na、Suzuki Takashi、Tavosanis Gaia、Sugie Atsushi
    • Journal Title

      BioRxiV

      Volume: -

    • DOI

      10.1101/2021.10.25.465674

    • Related Report
      2021 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Glial insulin regulates cooperative or antagonistic Golden goal/Flamingo interactions during photoreceptor axon guidance2021

    • Author(s)
      Takechi Hiroki、Hakeda-Suzuki Satoko、Nitta Yohei、Ishiwata Yuichi、Iwanaga Riku、Sato Makoto、Sugie Atsushi、Suzuki Takashi
    • Journal Title

      eLife

      Volume: 10

    • DOI

      10.7554/elife.66718

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 博士後期課程入学者数と教員の研究業績の 関連性に関する探索的研究 ―新潟大学大学院自然科学研究科博士後期課程の事例分析―2021

    • Author(s)
      新田 陽平、船山 理恵、杉江 淳、平井 克之
    • Journal Title

      新潟大学高等教育研究

      Volume: 8 Pages: 1-8

    • NAID

      120007177265

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Degeneration of dopaminergic neurons and impaired intracellular trafficking in Atp13a2 deficient zebrafish2020

    • Author(s)
      Nyuzuki Hiromi、Ito Shinji、Nagasaki Keisuke、Nitta Yohei、Matsui Noriko、Saitoh Akihiko、Matsui Hideaki
    • Journal Title

      IBRO Reports

      Volume: 9 Pages: 1-8

    • DOI

      10.1016/j.ibror.2020.05.002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysing the evolutional and functional differentiation of four types of Daphnia magna cryptochrome in Drosophila circadian clock2019

    • Author(s)
      Yohei Nitta, Sayaka Matsui, Yukine Kato, Yosuke Kaga, Kenkichi Sugimoto & Atsushi Sugie
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 8857-8857

    • DOI

      10.1038/s41598-019-45410-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] MeDUsA:A novel method for quantification of degeneration using fly axons to evaluate neuroaxonal degeneration2021

    • Author(s)
      新田陽平
    • Organizer
      第14回日本ショウジョウバエ研究集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Semi-automated quantitative system for neurodegeneration reveals the axonal degeneration by the Impaired PtdIns(4,5)P2 synthesis in Drosophila photoreceptor axons2020

    • Author(s)
      Yohei Nitta, Hiroki Kawai, Yosuke Kaga, Atsushi Sugie
    • Organizer
      Neuro2020
    • Related Report
      2020 Research-status Report
  • [Presentation] Impaired PtdIns(4,5)P2 synthesis in Drosophila neurons causes Calpain-dependent neurodegeneration2020

    • Author(s)
      Yohei Nitta, Atsushi Sugie
    • Organizer
      BRI 10th The International Symposium
    • Related Report
      2019 Research-status Report
  • [Presentation] CdsA, CDP-diacylglycerol synthase, protects neurons from degeneration through PI(4,5)P2-dependent mechanisms in Drosophila2019

    • Author(s)
      Yohei Nitta, Atsushi Sugie
    • Organizer
      NEURO2019
    • Related Report
      2019 Research-status Report
  • [Presentation] DISCO Interacting Protein 2 regulates multiple aspects of the development of axonal branches in Drosophila mushroom body neurons2018

    • Author(s)
      Yohei Nitta, Daisuke Yamazaki, Atsushi Sugie, Makoto Hiroi, Tetsuya Tabata
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Loss of CdsA, CDP-diacylglycerol synthetase, causes neurodegeneration in mushroom body through phosphatidylinositol pathway2018

    • Author(s)
      Yohei Nitta, Atsushi Sugie
    • Organizer
      JDRC13
    • Related Report
      2018 Research-status Report
  • [Remarks] 新たなARF3の遺伝子変異を発見

    • URL

      https://www.bri.niigata-u.ac.jp/research/result/001570.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] ショウジョウバエを利用したミジンコのクリプトクロームの進化的および機能的分化の解析

    • URL

      https://www.bri.niigata-u.ac.jp/result/neuroscience/001200.html

    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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