• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pathophysiology and therapeutic development of mitochondrial axonal transport disorders using Drosophila model of neurological diseases

Research Project

Project/Area Number 19K16924
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Kitani-Morii Fukiko  京都府立医科大学, 医学(系)研究科(研究院), 助教 (60806842)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords疾患モデル / 神経変性疾患 / ショウジョウバエ / シャルコー・マリー・トゥース病 / CMT2A / キネシン
Outline of Research at the Start

ミトコンドリア機能障害は様々な神経変性疾患を引き起こすことが知られているが、遺伝性の末梢神経障害を特徴とするCharcot-Marie-Tooth病タイプ2A(CMT2A)はミトコンドリア外膜蛋白のミトフシン2(MFN2)遺伝子変異によって生じ、ミトコンドリアと神経疾患をつなぐモデルとして注目されている。本研究では変異MFN2によるミトコンドリア軸索輸送障害の機序解明と新規治療標的の開発を目的とする。申請者はショウジョウバエを用いた疾患モデルとCMT患者iPS細胞由来神経細胞モデルを用いてその詳細を明らかにし、薬剤スクリーニングを行う。

Outline of Final Research Achievements

The aim of this study was to identify molecules involved in mitochondrial axonal transport, analyze their functions, and develop therapeutic strategies. Similarly, motor function was improved in an amyotrophic lateral sclerosis model.In Drosophila, a neural-specific human TDP43 transgenic strain, mating with the Klp68D-KD strain also prolonged survival.Comprehensive gene expression analysis showed a significant down-regulation of Hsp70, and oral administration of an Hsp70 inhibitor tended to improve locomotor function in adults, but the difference did not reach statistical significance.

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患においてミトコンドリアの軸索輸送は長い神経の末端までエネルギーを供給するシステムとして重要であるが、その運搬に関与する具体的な分子は不明点が多かった。本研究でショウジョウバエKlp68D(ヒトKif3Bホモログ)は複数の運動神経変性疾患の原因遺伝子と遺伝的相互作用を示し、発現抑制によって予後の改善が得られた。さらにHsp70の関与が示された。複数の異なる遺伝子で共通に変化する分子の同定に至ったことにより幅広い神経変性疾患への応用が可能な治療標的となり得る

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (4 results)

All 2021 2020

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

  • [Journal Article] Drosophila as a Model for Microbiota Studies of Neurodegeneration2021

    • Author(s)
      Kitani-Morii Fukiko、Friedland Robert P.、Yoshida Hideki、Mizuno Toshiki
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 84 Issue: 2 Pages: 479-490

    • DOI

      10.3233/jad-215031

    • Related Report
      2021 Research-status Report
  • [Journal Article] Recent Advances in Drosophila Models of Charcot-Marie-Tooth Disease2020

    • Author(s)
      Kitani-Morii Fukiko、Noto Yu-ichi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 19 Pages: 7419-7419

    • DOI

      10.3390/ijms21197419

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Investigating Kinesins as potential therapeutic targets of axonal degeneration using Drosophila models2020

    • Author(s)
      Fukiko Kitani-Morii
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Investigating Kinesins as potential therapeutic targets of CMT and ALS using Drosophila model2020

    • Author(s)
      Fukiko Kitani-Morii
    • Organizer
      Peripheral Nerve Society 2020 Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi