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Lysosomal dysfunction and its pharmacological treatment in autism spectrum disorders

Research Project

Project/Area Number 18K07592
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionKanazawa University

Principal Investigator

朱 紅  金沢大学, 子どものこころの発達研究センター, 博士研究員 (90778614)

Project Period (FY) 2018-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords自閉スペクトラム症 / ミクログリア / 発達障害 / 社会性行動 / ライソゾーム
Outline of Annual Research Achievements

糖タンパクGpnmb (glycoprotein nonmetastatic melanoma b)はマクロファージ、ミクログリア、樹状細胞(dendritic cell)および未分化なグリオーマ細胞に高発現する。Gpnmbは推定膜貫通領域を一つもち、ライソゾーム標識抗原CD68(ED1)などと同時局在する。この糖タンパクが神経系の発達・成長に果たす役割を調べるために、大量かつ高純度の組換え型Gpnmbタンパクを得ることを目指している。ラットGpnmbをコードするcDNAを発現ベクターに繋いで大腸菌に導入し、大量発現・精製する実験に取り組んだ結果、推定膜貫通領域およびカルボキシル末端を除いた部分を融合タンパクとして大量発現させることに成功した。しかしながら、その後、高純度に精製する条件の最適化を試みたが、適切な方法を見つけられないままであった。そこで、哺乳類細胞であるExpi発現システムを試したところ、このシステムでも高い発現レベルを得られることが判った。糖鎖付加がタンパク機能に与える影響があるかも知れないことも考慮すると、発現系を大腸菌から哺乳類細胞に切り替えることの優位性が予想されたので、Expi293F細胞に発現させたGpnmbタンパクの大量精製を進めることに方針を変更した。昨年度に続き、Expi293F細胞からの大量精製する各種条件を試とともに、神経系細胞の培養を開始し、Gpnmbタンパクが初代培養ニューロンおよび神経由来培養細胞株の電気的膜興奮性・分化・増殖に与える影響、およびミクログリアのライソゾームの機能調節作用をもつか否かを調べる準備に取りかかっている。

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

哺乳類Expi293F細胞に発現させたGpnmbタンパクの精製条件の決定に時間がかかっている。

Strategy for Future Research Activity

組換え型Gpnmbタンパクの精製方法・条件を繰り返し、最適化する。神経系培養細胞に添加した時の神経突起伸長性と遊走性を中心とした変化を調べる。またミクログリアにおいて、siRNAによるGpnmb抑制がライソゾーム安定性に与える影響を調べる。

Report

(6 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Sex Differences in Salivary Oxytocin and Cortisol Concentration Changes during Cooking in a Small Group2018

    • Author(s)
      Yuhi Teruko、Ise Kosuke、Iwashina Kei、Terao Naoya、Yoshioka Satoshi、Shomura Keijiro、Maehara Toshikatsu、Yazaki Akari、Koichi Kana、Furuhara Kazumi、Cherepanov Stanislav、Gerasimenko Maria、Shabalova Anna、Hosoki Kouhei、Kodama Hikari、Zhu Hong、Tsuji Chiharu、Yokoyama Shigeru、Higashida Haruhiro
    • Journal Title

      Behavioral Sciences

      Volume: 8 Issue: 11 Pages: 101-101

    • DOI

      10.3390/bs8110101

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Glycoprotein non-metastatic melanoma B in the developing rat brain: possible involvement in neural development.2021

    • Author(s)
      Hong Zhu, Eikichi Kamimura, Asep Saefulloh, Shigeru Yokoyama
    • Organizer
      日本生化学会北陸支部第39回大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Gene expression analysis of the fetal brain of rats following maternal poly I:C exposure during pregnancy.2020

    • Author(s)
      Asep Saefulloh, Eikichi Kamimura, Hong Zhu, Shin-ichi Horike and Shigeru Yokoyama
    • Organizer
      日本生化学会北陸支部第38回大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Gene Expression Analysis of the Fetal Brain of Rats Following Maternal Poly I:C Exposure during Pregnancy.2020

    • Author(s)
      Saefulloh A, Kamimura E, Zhu H, Horike S-I and Yokoyama S.
    • Organizer
      New Frontier in Neuroscience 2020: International Symposium on Neural Development, Regeneration & Disease (Kanazawa University Chozen Project)
    • Related Report
      2019 Research-status Report
  • [Presentation] Behavioral analysis of rat offspring following maternal immune activation in late pregnancy.2020

    • Author(s)
      Kamimura E, Saefulloh A, Zhu H and Yokoyama S.
    • Organizer
      New Frontier in Neuroscience 2020: International Symposium on Neural Development, Regeneration & Disease (Kanazawa University Chozen Project)
    • Related Report
      2019 Research-status Report
  • [Presentation] Glycoprotein non-metastatic melanoma B in the developing rat brain: possible involved in neural development.2020

    • Author(s)
      Zhu H, Kamimura E, Saefulloh A and Yokoyama S.
    • Organizer
      New Frontier in Neuroscience 2020: International Symposium on Neural Development, Regeneration & Disease (Kanazawa University Chozen Project)
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of maternal poly I:C exposure on gene expression patterns in the fetal brain of rats.2019

    • Author(s)
      Saefulloh A, Kamimura E, Zhu H, and Yokoyama S.
    • Organizer
      The 46thAnnual Meeting of the Japan Brain Science Society
    • Related Report
      2019 Research-status Report
  • [Presentation] Altered gene expression in the embryonic rat brain following maternal poly I:C exposure during pregnancy.2019

    • Author(s)
      Kamimura E, Zhu H, Saefulloh A and Yokoyama S.
    • Organizer
      The 49th Annual Meeting of Society for Neuroscience
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Developmental changes in Gpnmb expression in the prenatal rat brain2018

    • Author(s)
      Yokoyama Shigeru、Zhu Hong.
    • Organizer
      The 48th Annual Meeting of Society for Neuroscience
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2024-12-25  

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