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Analysis of host genetic factors associated with disease suppression against prion diseases.

Research Project

Project/Area Number 16H05317
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTohoku University

Principal Investigator

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

Research Collaborator TERUYA Kenta  
NISHIZAWA Keiko  
OGUMA Ayumi  
SAKASEGAWA Yuji  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords遺伝子 / ゲノム / 脳神経疾患 / マイクロアレイ / プリオン
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 effects against prions for a long period of time. The CE effectiveness is clearly dependent on mouse strains. In the current study, we found that there was no difference in the pharmacokinetics of CE between high-sensitive mice and low-sensitive mice. Then, we searched for host factors affecting sensitivity in the offspring from high-sensitive mice and low-sensitive mice. Finally, as a result, we found that a polymorphism of a certain glial related gene is associated with sensitivity. The findings open a new avenue of elucidating anti-prion defense mechanism and overcoming prion disease.

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感受性候補因子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)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (26 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Int'l Joint Research: 12 results,  Invited: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (3 results)

  • [Int'l Joint Research] University of Calgary(カナダ)

    • Related Report
      2018 Annual Research Report
  • [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
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intermolecular crosslinking of abnormal prion protein is efficiently induced by a primuline-sensitized photoreaction2019

    • Author(s)
      Teruya Kenta、Nishizawa Keiko、Oguma Ayumi、Sakasegawa Yuji、Kitamoto Tetsuyuki、Doh-ura Katsumi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1863 Issue: 2 Pages: 384-394

    • DOI

      10.1016/j.bbagen.2018.11.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pyrene conjugation and spectroscopic analysis of hydroxypropyl methylcellulose compounds successfully demonstrated a local dielectric difference associated with in vivo anti-prion activity.2017

    • Author(s)
      Teruya K, Oguma A, Nishizawa K, Kamitakahara H, Doh-ura K.
    • Journal Title

      PLoS One.

      Volume: 12(9) Issue: 9 Pages: e0185357-e0185357

    • DOI

      10.1371/journal.pone.0185357

    • NAID

      120006878530

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] プリオン病の多様性と治療開発2017

    • Author(s)
      逆瀬川 裕二、堂浦 克美
    • Journal Title

      実験医学 増刊

      Volume: 35(12) Pages: 27-35

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Melanin or melanin-like substance interacts with the N-terminal portion of prion protein and inhibits abnormal prion protein formation in prion-infected cells.2017

    • Author(s)
      Taichi Hamanaka, Keiko Nishizawa, Yuji Sakasegawa, Ayumi Oguma, Kenta Teruya, Hiroshi Kurahashi, Hideyuki Hara, Suehiro Sakaguchi, Katsumi Doh-ura
    • Journal Title

      Journal of Virology

      Volume: 印刷中 Issue: 6

    • DOI

      10.1128/jvi.01862-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insights from Therapeutic Studies for PrP Prion Disease.2017

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

      Cold Spring Harb Perspect Med.

      Volume: 7(3) Issue: 3 Pages: a024430-a024430

    • DOI

      10.1101/cshperspect.a024430

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 「プリオン病のアミロイドーシス」最新アミロイドーシスのすべて2017

    • Author(s)
      照屋健太、堂浦克美
    • Journal Title

      医師薬出版

      Volume: - Pages: 226-236

    • Related Report
      2016 Annual Research Report
  • [Journal Article] A Single Subcutaneous Injection of Cellulose Ethers Administered Long before Infection Confers Sustained Protection against Prion Diseases in Rodents.2016

    • Author(s)
      Teruya K, Oguma A, Nishizawa K, Kawata M, Sakasegawa Y, Kamitakahara H, Doh-ura K.
    • Journal Title

      PLoS Pathog.

      Volume: 12(12) Issue: 12 Pages: e1006045-e1006045

    • DOI

      10.1371/journal.ppat.1006045

    • NAID

      120005980891

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Photoreaction-induced SDS-resistant PrP Sc/res oligomer formation.2018

    • Author(s)
      Teruya K, Nishizawa K, Oguma A, Sakasegawa Y, Doh-ura K.
    • Organizer
      Asian Pacific Prion Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Liposomal formulation improved the anti-prion activity of cellulose ether compounds in ScN2a cells.2018

    • Author(s)
      Nishizawa K, Teruya K, Oguma A, Sakasegawa Y, Doh-ura K.
    • Organizer
      Asian Pacific Prion Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A platinum compound enhances the endogenous proteolytic degradation of the PrPC and PrPres in mouse neuroblastoma N2a cells.2018

    • Author(s)
      Sakasegawa Y, Nishizawa K, Oguma A, Teruya K, Doh-ura K.
    • Organizer
      Asian Pacific Prion Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cellulose ether compounds exert protection to prion infection; a biological parameter related to the effectiveness of compounds.2017

    • Author(s)
      Doh-ura K, Teruya K, Nishizawa K, Oguma A, Sakasegawa Y, Kamitakahara H.
    • Organizer
      Asian Pacific Prion Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pyrene index of hydroxypropyl methylcellulose compounds correlates with the in vivo long-lasting anti-prion activity.2017

    • Author(s)
      Teruya K, Oguma A, Nishizawa K, Kamitakahara H, Doh-ura K.
    • Organizer
      Asian Pacific Prion Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Anti-prion activities of cellulose ether compounds in prion-infected cells are consistent with long-lasting anti-prion activities in vivo.2017

    • Author(s)
      Nishizawa K, Teruya K, Oguma A, Sakasegawa Y, Doh-ura K.
    • Organizer
      Asian Pacific Prion Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] C-terminal chaperone domain of heat shock protein 90 modifies the conformation of cellular prion protein central region in the presence of copper ion.2017

    • Author(s)
      Sakasegawa Y, Nishizawa K, Oguma A, Teruya K, Doh-ura K.
    • Organizer
      Asian Pacific Prion Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Protein Aggregation - Prions: still untouchable agents -.2017

    • Author(s)
      Doh-ura K.
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] プリオン病の原因であるPrPScは排除が困難2016

    • Author(s)
      堂浦 克美
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台、仙台国際センター
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Lessons from recent outcomes of clinical trials and therapeutic studies.2016

    • Author(s)
      Doh-ura K.
    • Organizer
      PRION2016TOKYO
    • Place of Presentation
      東京、一ツ橋ホール
    • Year and Date
      2016-05-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dimer-sized PrPSc formation detected by western blotting.2016

    • Author(s)
      Teruya K, Doh-ura K.
    • Organizer
      PRION2016TOKYO
    • Place of Presentation
      東京、一ツ橋ホール
    • Year and Date
      2016-05-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A platinum compound targeting the cysteine residues of disease-related form of prion protein in cell lysates.2016

    • Author(s)
      Sakasegawa Y, Doh-ura K.
    • Organizer
      PRION2016TOKYO
    • Place of Presentation
      東京、一ツ橋ホール
    • Year and Date
      2016-05-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of cell growth suppression treatments on PrPSc accumulation in prion-infected cells; Paradoxical phenomena observed in butyric acid treatment.2016

    • Author(s)
      Hiyoshi T, Doh-ura K.
    • Organizer
      PRION2016TOKYO
    • Place of Presentation
      東京、一ツ橋ホール
    • Year and Date
      2016-05-10
    • Related Report
      2016 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/index.html

    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] コンフォメーション病の予防又は治療剤、及びコンフォメーション病医薬のスクリーニング方法2018

    • Inventor(s)
      照屋 健太、西澤 桂子、堂浦 克美、
    • Industrial Property Rights Holder
      照屋 健太、西澤 桂子、堂浦 克美、
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] コンフォメーション病治療用材料、及びその製造方法、並びにコンフォメーション病医薬のスクリーニング方法2017

    • Inventor(s)
      堂浦 克美、照屋 健太
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-169312
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] コンフォメーション病医薬組成物及びその製造方法2016

    • Inventor(s)
      堂浦 克美、照屋 健太、西澤 桂子、小熊 歩
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-05-09
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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