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Development of novel treatment against peroxiredoxin in central nervous system demyelinating diseases

Research Project

Project/Area Number 16K09691
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionChiba University

Principal Investigator

Uzawa Akiyuki  千葉大学, 医学部附属病院, 助教 (10533317)

Co-Investigator(Kenkyū-buntansha) 桑原 聡  千葉大学, 大学院医学研究院, 教授 (70282481)
森 雅裕  千葉大学, 大学院医学研究院, 准教授 (70345023)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords多発性硬化症 / 視神経脊髄炎 / 動物モデル / ペルオキシレドキシン / 炎症 / サイトカイン / 新規治療 / CD45 / EAE / 免疫染色 / 髄液 / 神経科学 / 神経免疫 / 損傷関連分子パター
Outline of Final Research Achievements

The concentrations of peroxiredoxins 1, 5 and 6 in the serum and cerebrospinal fluid in the acute phase of central nervous inflammatory demyelinating diseases (neuromyelitis optica and multiple sclerosis) were measured. Moreover, the immunostaining of peroxiredoxin 1-6 was performed using the spinal cord of EAE mouse (an animal model of MS). As a result, serum peroxyredoxins 5 and 6 were significantly elevated in central nervous inflammatory demyelinating disease than disease control, but no significant changes of peroxyredoxins was observed in cerebrospinal fluid. Moreover, peroxiredoxin 5 was abundantly expressed in CD45 positive cells, which were accumulated in the spinal cord lesion of EAE mice.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から炎症誘導因子の一つであるペルオキシレドキシンは中枢神経炎症性脱髄疾患において有意に変化しており、病変部に集積しているCD45陽性細胞が、ペルオキシレドキシンを介して炎症反応を惹起し病態に強く関与している可能性が高いと考えられた。今後ペルオキシレドキシンを治療ターゲットとした新規治療開発へと応用できる可能性がある。

Report

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

    (27 results)

All 2019 2018 2017 2016 Other

All Journal Article (18 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 18 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

  • [Journal Article] Serum anti-JCV antibody indexes in Japanese patients with multiple sclerosis: elevations along with fingolimod treatment duration2018

    • Author(s)
      Aoyama Shinji、Mori Masahiro、Uzawa Akiyuki、Uchida Tomohiko、Masuda Hiroki、Ohtani Ryohei、Kuwabara Satoshi
    • Journal Title

      J Neurol

      Volume: in press Issue: 5 Pages: 1145-1150

    • DOI

      10.1007/s00415-018-8813-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recombinant thrombomodulin ameliorates experimental autoimmune encephalomyelitis by suppressing HMGB1 and inflammatory cytokines2018

    • Author(s)
      Uzawa Akiyuki、Mori Masahiro、Masuda Hiroki、Ohtani Ryohei、Uchida Tomohiko、Kuwabara Satoshi
    • Journal Title

      Clin Exp Immunol

      Volume: in press Issue: 1 Pages: 47-54

    • DOI

      10.1111/cei.13123

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk factors for fingolimod-induced lymphopenia in multiple sclerosis2018

    • Author(s)
      Ohtani Ryohei、Mori Masahiro、Uchida Tomohiko、Uzawa Akiyuki、Masuda Hiroki、Liu Jia、Kuwabara Satoshi
    • Journal Title

      Mult Scler J Exp Transl Clin

      Volume: 4 Issue: 1 Pages: 205521731875969-205521731875969

    • DOI

      10.1177/2055217318759692

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Validation of the Modified Fatigue Impact Scale and the relationships among fatigue, pain and serum interleukin-6 levels in patients with neuromyelitis optica spectrum disorder2018

    • Author(s)
      Masuda Hiroki、Mori Masahiro、Uzawa Akiyuki、Uchida Tomohiko、Ohtani Ryohei、Kobayashi Shigeo、Kuwabara Satoshi
    • Journal Title

      J Neurol Sci

      Volume: 385 Pages: 64-68

    • DOI

      10.1016/j.jns.2017.11.041

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Soluble CD40 ligand disrupts the blood?brain barrier and exacerbates inflammation in experimental autoimmune encephalomyelitis2018

    • Author(s)
      Masuda Hiroki、Mori Masahiro、Umehara Kenta、Furihata Tomomi、Uchida Tomohiko、Uzawa Akiyuki、Kuwabara Satoshi
    • Journal Title

      J Neuroimmunol

      Volume: 316 Pages: 117-120

    • DOI

      10.1016/j.jneuroim.2018.01.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oral corticosteroid dosing regimen and long-term prognosis in generalised myasthenia gravis: a multicentre cross-sectional study in Japan2018

    • Author(s)
      Imai Tomihiro、Utsugisawa Kimiaki、Murai Hiroyuki、Tsuda Emiko、Nagane Yuriko、Suzuki Yasushi、Minami Naoya、Uzawa Akiyuki、Kawaguchi Naoki、Masuda Masayuki、Konno Shingo、Suzuki Hidekazu、Akaishi Tetsuya、Aoki Masashi
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: in press Issue: 5 Pages: 513-517

    • DOI

      10.1136/jnnp-2017-316625

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction2017

    • Author(s)
      Wang H,Zhang X-M,Tomiyoshi G,Nakamura R,Shinmen N,Kuroda H,Kimura R,Mine S,Kamitsukasa I,Wada T,Aotsuka A,Yoshida Y,Kobayashi E,Matsutani T,Iwadate Y,Sugimoto K,Mori M,Uzawa A,Muto M,Kuwabara S,Takemoto M,Kobayashi K,Kawamura H,Ishibashi R,Yokote K,Ohno M,
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 5 Pages: 5600-5613

    • DOI

      10.18632/oncotarget.23789

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A clinical predictive score for postoperative myasthenic crisis2017

    • Author(s)
      Kanai Tetsuya、Uzawa Akiyuki、et al.
    • Journal Title

      Ann Neurol

      Volume: 82 Issue: 5 Pages: 841-849

    • DOI

      10.1002/ana.25087

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of cognitive and brain grey matter volume profiles between multiple sclerosis and neuromyelitis optica spectrum disorder2017

    • Author(s)
      Masuda Hiroki、Hirano Shigeki、Takahashi Nobuyoshi、Hatsugano Etsuko、Uzawa Akiyuki、Uchida Tomohiko、Ohtani Ryohei、Kuwabara Satoshi、Mori Masahiro
    • Journal Title

      PLoS One

      Volume: 12 Issue: 8 Pages: e0184012-e0184012

    • DOI

      10.1371/journal.pone.0184012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Geographical differences in preventative therapies for neuromyelitis optica spectrum disorder2017

    • Author(s)
      Mori Masahiro、Uzawa Akiyuki、Kuwabara Satoshi
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 88 Issue: 8 Pages: 620-620

    • DOI

      10.1136/jnnp-2017-315769

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum soluble Talin-1 levels are elevated in patients with multiple sclerosis, reflecting its disease activity.2017

    • Author(s)
      Mayumi Muto, Masahiro Moti, Jia Liu, Tomohiko Uchida, Hiroki Masuda, Ryohei Ohtani, Kazuo Sugimoto, Sathoshi Kuwabara
    • Journal Title

      Journal of Neuroimmunology

      Volume: 305 Pages: 131-134

    • DOI

      10.1016/j.jneuroim.2017.02.008

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Soluble CD40 ligand contributes to blood brain barrier breakdown and central nervous system inflammation in multiple sclerosis and neuromyelitis optica spectrum disorder2017

    • Author(s)
      Masuda H, Mori M, Uchida T, Uzawa A, Ohtani R, Kuwabara S.
    • Journal Title

      J Neuroimmnol

      Volume: 305 Pages: 102-107

    • DOI

      10.1016/j.jneuroim.2017.01.024

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-6 analysis of 572 consecutive CSF samples from neurological disorders: A special focus on neuromyelitis optica2017

    • Author(s)
      Uzawa A, Mori M, Masuda H, Ohtani R, Uchida T, Sawai S, Kuwabara S
    • Journal Title

      Clinica Chimica Acta

      Volume: in press Pages: 144-149

    • DOI

      10.1016/j.cca.2017.03.006

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased cerebrospinal fluid metalloproteinase-2 and interleukin-6 are associated with albumin quotient in neuromyelitis optica: Their possible role on blood-brain barrier disruption.2017

    • Author(s)
      Uchida T, Mori M, Uzawa A, Masuda H, Muto M, Ohtani R, Kuwabara S
    • Journal Title

      Mult Scler

      Volume: in press Issue: 8 Pages: 1072-1084

    • DOI

      10.1177/1352458516672015

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Early fast-acting treatment strategy against generalized myasthenia gravis2017

    • Author(s)
      Utsugisawa Kimiaki、Nagane Yuriko、Akaishi Tetsuya、Suzuki Yasushi、Imai Tomihiro、Tsuda Emiko、Minami Naoya、Uzawa Akiyuki、Kawaguchi Naoki、Masuda Masayuki、Konno Shingo、Suzuki Hidekazu、Murai Hiroyuki、Aoki Masashi
    • Journal Title

      Muscle Nerve

      Volume: 55 Issue: 6 Pages: 794-801

    • DOI

      10.1002/mus.25397

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroimmunology of a natural disaster2017

    • Author(s)
      Kuwabara Satoshi、Uzawa Akiyuki、Mori Masahiro
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 88 Issue: 4 Pages: 283-283

    • DOI

      10.1136/jnnp-2016-314198

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Seronegative neuromyelitis optica spectrum disorder patients diagnosed using new diagnostic criteria2016

    • Author(s)
      Uzawa A, Mori M, Uchida T, Masuda H, Ohtani R, Kuwabara S
    • Journal Title

      Mult Scler

      Volume: 22 Issue: 10 Pages: 1371-1375

    • DOI

      10.1177/1352458515615954

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased levels of CSF CD59 in neuromyelitis optica and multiple sclerosis2016

    • Author(s)
      Uzawa A, Mori M, Uchida T, Masuda H, Ohtani R, Kuwabara S
    • Journal Title

      Clinica Chimica Acta

      Volume: 453 Pages: 131-133

    • DOI

      10.1016/j.cca.2015.12.013

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 中枢神経炎症性脱髄疾患病態におけるペルオキシレドキシンの関与2019

    • Author(s)
      鵜沢顕之
    • Organizer
      日本神経学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CSF CD59 UPREGULATION IN NEUROMYELITIS OPTICA AND MULTIPLE SCLEROSIS2017

    • Author(s)
      Akiyuki Uzawa
    • Organizer
      International Taiwanese Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] CSF IL-6 study in neurological disorders with a special focus on neuromyelitis optica2017

    • Author(s)
      Akiyuki Uzawa
    • Organizer
      World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] リコンビナントトロンボモジュリンの多発性硬化症治療への応用2017

    • Author(s)
      鵜沢顕之
    • Organizer
      日本神経免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 重症筋無力症の革新的治療法:融合蛋白AChR-Fc2017

    • Author(s)
      鵜沢顕之
    • Organizer
      日本神経治療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 重症筋無力症におけるダメージ関連分子パターンとサイトカインの関連2016

    • Author(s)
      鵜沢顕之、金井哲也、川口直樹、織田史子、小澤由希子、氷室圭一、桑原聡
    • Organizer
      日本神経免疫学会学術集会
    • Place of Presentation
      長崎ブリックホール(長崎県、長崎市)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] Implication of damage-associated molecular patterns in myasthenia gravis2016

    • Author(s)
      Akiyuki Uzawa, Tetsuya Kanai, Naoki Kawaguchi, Fumiko Oda, Yukiko Ozawa, Keiichi Himuro, Satoshi Kuwabara
    • Organizer
      the 15th Asian and Oceanian Congress of Neurology
    • Place of Presentation
      Kuala Lumpur City Centre (Kuala Lumpur, Malaysia)
    • Year and Date
      2016-08-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 千葉大学大学院医学研究院神経内科学

    • URL

      http://www.m.chiba-u.ac.jp/dept/neurol/

    • Related Report
      2017 Research-status Report
  • [Remarks] 千葉大学大学院医学研究院 神経内科学

    • URL

      http://www.m.chiba-u.jp/class/neurol/

    • Related Report
      2016 Research-status Report

URL: 

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

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