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Schwann cell abnormality due to variant TTR and neurodegeneration

Research Project

Project/Area Number 16K09686
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKawasaki Medical School

Principal Investigator

Tatsufumi Murakami  川崎医科大学, 医学部, 准教授 (30330591)

Co-Investigator(Kenkyū-buntansha) 砂田 芳秀  川崎医科大学, 医学部, 教授 (00240713)
大澤 裕  川崎医科大学, 医学部, 講師 (80246511)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords異型トランスサイレチン / シュワン細胞 / 感覚神経細胞 / 神経変性 / アミロイド / アグリソーム / アポトーシス / 熱ショック因子1 / プロテオソーム阻害剤 / 神経突起成長 / グリア神経細胞連関 / 脳神経疾患 / 神経科学
Outline of Final Research Achievements

TgS1 Schwann cells, which are derived from a FAP transgenic mouse expressing V30M TTR gene. were treated with a proteasome inhibitor, resulting in granular vesicle formation as an aggresome. TgS1 were also treated with Hsf1 siRNA, and the swelling snd filling with TTR were recognized in the cytoplasms and the dendrites of the cells.
Neurite-growth assay was performed using rat DRG neurons with wild-type TTR and V30M TTR. V30M TTR inhibited the neuritis outgrowth, but wild-type TTR did not. Immnohistochemistry of the sural nerve specimen of a FAP TTR E61K patient demonstrated several TTR positive Schwann cells in the peripheral nerve.

Academic Significance and Societal Importance of the Research Achievements

家族性アミロイドポリニューロパチー(FAP)は末梢神経へのアミロイド沈着を特徴とする。本研究では疾患モデルTgS1シュワン培養細胞を用い、TTR凝集機序を調べた。その結果TgS1細胞の熱ストレス応答を低下させると、細胞内TTR凝集が著しく増加することを見出した。この事はシュワン細胞の蛋白品質管理の低下が、細胞内でTTR凝集を生じさせ、末梢神経でのアミロイド沈着の契機となっているかも知れないことを示唆した。シュワン細胞がFAP治療の標的となるかも知れない。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2019 2018 2017 2016 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (9 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

  • [Journal Article] Transthyretin amyloid neuropathy: the Schwann cell hypothesis2019

    • Author(s)
      Tatsufumi Murakami, Yoshihde Sunada
    • Journal Title

      Myelin - Basic and Clinical Advances

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and pathological findings in familial amyloid polyneuropathy caused by a transthyretin E61K mutation2017

    • Author(s)
      Tatsufumi Murakami, Hirotake Nishimura, Taiji Nagai, Shoji Hemmi, Yumiko Kutoku, Yutaka Ohsawa, Yoshihide Sunada
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 381 Pages: 55-58

    • DOI

      10.1016/j.jns.2017.08.017

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] TTR型アミロイドーシスでの末梢神経障害機序の研究 :シュワン細胞の関与について2016

    • Author(s)
      村上龍文、三五一憲、渡部和彦、新見直子、 李正花、山村研一、砂田芳秀
    • Journal Title

      Peripheral Nerve

      Volume: 27(1) Pages: 62-67

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Amyloidogenicity of E61K TTR associated with TTR amyloid neuropathy.2019

    • Author(s)
      Tatsufumi Murakami, Mineykuki Mizuguchi, Kazunori Sango, Shigenobu Tone, Yoshihide Sunada
    • Organizer
      60th Annual Meeting of the Japanese Society of Neurology, 2019 5. 25, Osaka
    • Related Report
      2018 Annual Research Report
  • [Presentation] 家族性アミロイドポリニューロパチーTTR E61Kの神経変性機序の研究:神経細胞障害の検討2019

    • Author(s)
      村上龍文、刀祢重信、三五一憲、新見直子, 水口峰之、砂田芳秀
    • Organizer
      第30回日本末梢神経学会、2019. 8. 23-24, 金沢
    • Related Report
      2018 Annual Research Report
  • [Presentation] 家族性アミロイドポリニューロパチー TTR E61Kの神経変性機序の研究:アミロイド凝集能の検討.2018

    • Author(s)
      村上龍文、刀祢重信、三五一憲、渡部和彦, 水口峰之、砂田芳秀
    • Organizer
      第29回日本末梢神経学会, 2018. 9. 8, 下関
    • Related Report
      2018 Annual Research Report
  • [Presentation] Clinical and pathological findings in familial amyloid polyneuropathy due to transthyretin E61K2017

    • Author(s)
      Tatsufumi Murakami, Hirotake Nishimura, Taiji Nagai, Shoji Hemmi, Yumiko Kutoku, Yutaka Ohsawa, Yoshihide Sunada
    • Organizer
      2017 PNS Annual meeting (July 8-12, in Sitges near Barcelona)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Neuropathological features in familial amyloid polyneuropathy caused by transthyretin E61K variant2017

    • Author(s)
      Tatsufumi Murakami, Hirotake Nishimura, Taiji Nagai, Shoji Hemmi, Yumiko Kutoku, Yutaka Ohsawa, Yoshihide Sunada
    • Organizer
      XXIII World Congress of Neurology (Sep 16-21, 2017, Kyoto)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] TTR E61Kによる家族性アミロイドポリニューロパチーの神経病理学的検討:初期病変はどこか?2017

    • Author(s)
      村上 龍文、西村広健、永井太士、逸見祥司、久徳弓子、 大澤 裕、砂田芳秀
    • Organizer
      第28回日本末梢神経学会(2017, 8.25-26, 名古屋)
    • Related Report
      2017 Research-status Report
  • [Presentation] Hereditary ataxic sensory neuropathy associated with proximal muscle weakness in the lower extremities: a new clinical entity?2016

    • Author(s)
      Murakami T, Morino H, Hemmi S, Kutoku Y, Ohsawa Y, Kawakami H, Sunada Y
    • Organizer
      6th International Charcot-Marie-Tooth and Related Neuropathy Consortium (CMTR) Meeting
    • Place of Presentation
      Venice
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] TTRアミロイドニューロパチーの神経障害発症機序の研究2016

    • Author(s)
      村上龍文、三五一憲、渡部和彦、新見直子、李正花、山村研一、砂田芳秀
    • Organizer
      第27回日本末梢神経学会
    • Place of Presentation
      大阪
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
  • [Presentation] TTR型アミロイドーシスの神経障害発生機序の研究:シュワン細胞の関与について2016

    • Author(s)
      村上龍文、三五一憲、渡部和彦、新見直子、山下倫太朗、李正花、山村研一、砂田芳秀
    • Organizer
      第57回日本神経学会
    • Place of Presentation
      神戸
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Remarks] 川崎医科大学神経内科学教室 研究のご紹介

    • URL

      http://www.kawasaki-m.ac/neurology/study/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 川崎医科大学神経内科学教室 研究のご紹介

    • URL

      http://www.kawasaki-m.ac.jp/neurology/study/index.html

    • Related Report
      2016 Research-status Report

URL: 

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

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