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Identification of cellulose ether susceptibility genes involved in suppression of prion disease development

Research Project

Project/Area Number 19H03570
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionTohoku University

Principal Investigator

Doh-ura Katsumi  東北大学, 医学系研究科, 教授 (00263012)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords遺伝子解析 / プロテオミクス解析 / プリオン / 防御機構 / セルロース誘導体 / 感受性 / gmfb / ゲノムマーカー
Outline of Research at the Start

本研究では、申請者がこれまで積み上げてきた独自の成果をさらに発展させる。すなわち、研究期間中に、日常摂取しているセルロース誘導体(CE)に応答してプリオンの増殖を長期間にわたり抑制するメカニズムに関わるCE感受性遺伝子を同定する研究を行う。研究の成果はCE効果の発現機序の解明に役立ち、これまで実体が捕らえられていなかったプリオンに対する生体防御機構の一端を解明することに繋がる。

Outline of Final Research Achievements

In our bodies, it is thought that prion proliferation is controlled under the influence of some external factors, but the mechanism is unknown. The applicant has found that a cellulose derivative (CE), which is ingested daily as a food additive, exhibits excellent suppressive effect against prion disease for a long period of time. The CE effectiveness is clearly dependent on mouse strains. In the current study, genomic and proteomic analyses were performed between different CE-susceptible mice to search for host factors that affect CE-susceptibility. As a result, we finally identified polymorphisms in the gmfb gene and neighboring genes as genomic markers of CE-susceptibility. These findings are expected to lead to the elucidation of defense mechanisms against prions and the overcoming of prion diseases.

Academic Significance and Societal Importance of the Research Achievements

特発性プリオン病に罹患するのはごく少数の人だけであり、また同様にプリオンに曝露されても発病しない人たちがいることがわかっており、私たちの体内には何らかの外的要因等を受けプリオンの増殖を抑制する防御機構が備わっている。CE感受性はまさにそういった防御機構の一部となっている可能性があり、CE感受性と密接に結び付くゲノムマーカーを明らかにした本研究成果は、プリオンに対する防御機構の解明やプリオン病の克服に繋がる知見である。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (22 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (8 results) (of which Int'l Joint Research: 4 results) Remarks (3 results)

  • [Int'l Joint Research] カルガリー大学(カナダ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] カルガリー大学(カナダ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Therapeutic development of polymers for prion disease.2022

    • Author(s)
      Teruya K, Doh-ura K.
    • Journal Title

      Cell Tissue Res.

      Volume: in press. Issue: 1 Pages: 349-365

    • DOI

      10.1007/s00441-022-03604-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-prion activity of cellulose ether is impaired in mice lacking pre T-cell antigen receptor α, T-cell receptor δ, or lytic granule function2022

    • Author(s)
      Teruya Kenta、Oguma Ayumi、Takahashi Satoko、Watanabe-Matsui Miki、Tsuji-Kawahara Sachiyo、Miyazawa Masaaki、Doh-ura Katsumi
    • Journal Title

      International Immunopharmacology

      Volume: 107 Pages: 108672-108672

    • DOI

      10.1016/j.intimp.2022.108672

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activities of curcumin-related compounds in two cell lines persistently infected with different prion strains2022

    • Author(s)
      Teruya Kenta、Iwabuchi Sara、Watanabe Yuki、Tsuchida Rikiya、Watanabe-Matsui Miki、Konno Hiroyuki、Doh-ura Katsumi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1866 Issue: 4 Pages: 130094-130094

    • DOI

      10.1016/j.bbagen.2022.130094

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decrease in Skin Prion-Seeding Activity of Prion-Infected Mice Treated with a Compound Against Human and Animal Prions: a First Possible Biomarker for Prion Therapeutics2021

    • Author(s)
      Ding Mingxuan、Teruya Kenta、Zhang Weiguanliu、Lee Hae Weon、Yuan Jue、Oguma Ayumi、Foutz Aaron、Camacho Manuel V.、Mitchell Marcus、Greenlee Justin J.、Kong Qingzhong、Doh-ura Katsumi、Cui Li、Zou Wen-Quan
    • Journal Title

      Molecular Neurobiology

      Volume: 58 Issue: 9 Pages: 4280-4292

    • DOI

      10.1007/s12035-021-02418-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polymorphisms in glia maturation factor β gene are markers of cellulose ether effectiveness in prion-infected mice2021

    • Author(s)
      Teruya Kenta、Oguma Ayumi、Arai Keita、Nishizawa Keikoi、Sakasegawa Yuji、Schatzl Hermann、、Iwabuchi Sara、Watanabe-Matsui MikGilch Sabine、Doh-ura Katsumi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 560 Pages: 105-111

    • DOI

      10.1016/j.bbrc.2021.04.116

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints.2020

    • Author(s)
      Minikel EV, Zhao HT, Le J, O'Moore J, Pitstick R, Graffam S, Carlson GA, Kavanaugh MP, Kriz J, Kim JB, Ma J, Wille H, Aiken J, McKenzie D, Doh-ura K, Beck M, O'Keefe R, Stathopoulos J, Caron T, Schreiber SL, Carroll JB, Kordasiewicz HB, Cabin DE, Vallabh SM.
    • Journal Title

      Nucleic Acids Res.

      Volume: 48(19) Issue: 19 Pages: 10615-10631

    • DOI

      10.1093/nar/gkaa616

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cellulose ether treatment in vivo generates chronic wasting disease prions with reduced protease resistance and delayed disease progression.2019

    • Author(s)
      Hannaoui S, Arifin MI, Chang SC, Yu J, Gopalakrishnan P, Doh-ura K, Schatzl HM, Gilch S.
    • Journal Title

      J Neurochem.

      Volume: 152(6) Issue: 6 Pages: 727-740

    • DOI

      10.1111/jnc.14877

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Combining autophagy stimulators and cellulose ethers for therapy against prion disease.2019

    • Author(s)
      Abdulrahman BA, Tahir W, Doh-ura K, Gilch S, Schatzl HM.
    • Journal Title

      Prion.

      Volume: (1) Issue: 1 Pages: 185-196

    • DOI

      10.1080/19336896.2019.1670928

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preparation and Characterization of Cellulose Ether Liposomes for the Inhibition of Prion Formation in Prion-infected Cells.2019

    • Author(s)
      Nishizawa K, Teruya K, Oguma A, Sakasegawa Y, Schatzl H, Gilch S, Doh-ura K.
    • Journal Title

      J Pharm Sci.

      Volume: - Issue: 8 Pages: 2814-2820

    • DOI

      10.1016/j.xphs.2019.03.025

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] フェロトーシス阻害剤による異常型プリオンタンパク質蓄積抑制機構の解明.2021

    • Author(s)
      松井 美紀、照屋 健太、小熊 歩、村山 和隆、堂浦 克美.
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Photoreaction-induced SDS-resistant PrPSc/res oligomer formation.2021

    • Author(s)
      Kenta Teruya, Toshiya Ishikawa, Sara Iwabuchi, Miki Watanabe-Matsui, Katsumi Doh-ura.
    • Organizer
      第58回ペプチド討論会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Prophylactic anti-prion effects of cellulose ether compounds depend on host mouse strains.2020

    • Author(s)
      Kenta Teruya, Keiko Nishizawa, Ayumi Oguma, Katsumi Doh-ura.
    • Organizer
      第57回ペプチド討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Characterization of the effects of curcumin related compounds on two prion strains.2020

    • Author(s)
      Sara Iwabuchi, Kenta Teruya, Miki Matsui, Hiroyuki Konno, Katsumi Doh-ura.
    • Organizer
      第57回ペプチド討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Protection to prion infection by cellulose ether compounds depends on host mouse strains.2019

    • Author(s)
      Teruya K, Nishizawa K, Oguma A, Sakasegawa Y, Kamitakahara H, Doh-ura K.
    • Organizer
      Asian Pacific Prion Symposium 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cellulose ether liposomes for the inhibition of prion formation.2019

    • Author(s)
      Nishizawa K, Teruya K, Oguma A, Sakasegawa Y, Kamitakahara H, Doh-ura K.
    • Organizer
      Asian Pacific Prion Symposium 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of cellulose ether liposomes for the inhibition of prion formation in prion-infected cells.2019

    • Author(s)
      Nishizawa K, Teruya K, Oguma A, Sakasegawa Y, Kamitakahara H, Schatzl H, Gilch S, Doh-ura K.
    • Organizer
      PRION2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cellulose ethers interfere with CWD prion propagation in vitro and in vivo.2019

    • Author(s)
      Gopalakrishnan P, Yu J, Hannaoui S, Chang SC, Arifin MI, Doh-ura K, Schatzl HM, Gilch S.
    • Organizer
      PRION2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 東北大学大学院 医学系研究科 神経化学分野

    • URL

      https://www.neurochemistry.med.tohoku.ac.jp/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科神経化学分野

    • URL

      https://www.neurochemistry.med.tohoku.ac.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 東北大学大学院医学系研究科神経化学分野

    • URL

      https://www.neurochemistry.med.tohoku.ac.jp/index.html

    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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