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Development of ALS therapy targeting LOTUS, a functional molecule for neuronal regeneration

Research Project

Project/Area Number 18K07532
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionYokohama City University

Principal Investigator

TANAKA Fumiaki  横浜市立大学, 医学研究科, 教授 (30378012)

Co-Investigator(Kenkyū-buntansha) 高橋 慶太  横浜市立大学, 附属病院, 助教 (20773740)
土井 宏  横浜市立大学, 医学部, 准教授 (10326035)
竹内 英之  横浜市立大学, 医学部, 准教授 (30362213)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsALS / LOTUS / Nogo / PIR-B
Outline of Final Research Achievements

In amyotrophic lateral sclerosis (ALS), the role of signal transduction via myelin-related neurite outgrowth inhibitors (MAIs) and their receptor NgR1 is attracting attention as its pathogenesis. Therefore, we investigated whether LOTUS, a molecule that inhibits the binding of MAIs and NgR1, could be a therapeutic target for ALS. Mating ALS model mice (mutated SOD1 (G93A) mice) with LOTUS transgenic mice improved motor function and prolonged survival of ALS mice. We will investigate the mechanism of this improvement and work on the development of ALS treatment targeting LOTUS.

Academic Significance and Societal Importance of the Research Achievements

筋萎縮性側索硬化症(ALS)は、運動ニューロンの障害により、数年で呼吸筋麻痺に至る致死的神経難病である。現在までのところ満足のいく治療法は開発されておらず、疾患の克服は喫緊の医学的課題である。治療法の開発には、ALSの病態を形成するキーとなる分子を標的とした創薬が求められるが、我々はLOTUSに着目した。ALSの病態には「神経変性」と「神経炎症」の二つの側面があるが、LOTUSはこれらを同時に制御しうる分子と考えられ、本研究により得られたLOTUSの治療効果は、今後の研究発展によりALSの克服に寄与することが期待される。

Report

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

    (2 results)

All 2021 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Ablation of interleukin-19 improves motor function in a mouse model of amyotrophic lateral sclerosis2021

    • Author(s)
      Komiya Hiroyasu、Takeuchi Hideyuki、Ogawa Yuki、Suzuki Kosuke、Ogasawara Akihiro、Takahashi Keita、Azuma Yasu-Taka、Doi Hiroshi、Tanaka Fumiaki
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 74-74

    • DOI

      10.1186/s13041-021-00785-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCR2 is localized in microglia and neurons, as well as infiltrating monocytes, in the lumbar spinal cord of ALS mice.2020

    • Author(s)
      Komiya H, Takeuchi H (責任著者), Ogawa Y, Hatooka Y, Takahashi K, Katsumoto A, Kubota S, Nakamura H, Kunii M, Tada M, Doi H, Tanaka F
    • Journal Title

      Molecular Brain

      Volume: 13 Issue: 1 Pages: 64-64

    • DOI

      10.1186/s13041-020-00607-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2018-04-23   Modified: 2022-01-27  

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