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Attempt to improve multiple sclerosis progression by the control of intestinal mitochondrial oxidative stress

Research Project

Project/Area Number 18K15452
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionOsaka University

Principal Investigator

Shimizu Mikito  大阪大学, 医学系研究科, 招へい教員 (30817507)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords多発性硬化症 / 活性酸素種 / 酸化ストレス / ミトコンドリア / 食事療法 / 視神経脊髄炎 / アストロサイト / 食事 / 腸管ミトコンドリア
Outline of Final Research Achievements

At first, we revealed that oral administration of succinic acid, which is contained as food additives, increases the ratio of TH17 cells, which induce inflammation and promote demyelination, to regulatory T cells, which suppress inflammation, through IL-1β release from immune cells. And also we demonstrated that the release of IL-1β is associated with an increase of mitochondrial reactive oxygen species (mitoROS) in immune cells.
Now, we are investigating the immune system alteration in the central nervous system through succinate acid administration, using human astrocytes and mouse primary astrocytes as in vitro experiments. And in vivo, we are also planning an immune cell transfer experiment in order to clarify succinate acid effects to immune system.

Academic Significance and Societal Importance of the Research Achievements

現在、多発性硬化症の治療薬は目覚しい進歩を遂げており、疾患コントロールはかなり改善されているが、重篤な副作用や、高額な医療費などまだまだ問題点も多い。またMRIの発達に症状が非常に軽微な時期から病変を検出することが可能となった一方、治療期間が延長する傾向にあることも、副作用や医療費の問題点を増大させている。今回提唱するような食事の工夫による免疫動態の制御が実現すれば、非常に安価で安全性の高い手段となるため、これらの現状を踏まえ必要性は増してくると思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Mitochondrial DNA enhance innate immune responses in neuromyelitis optica by monocyte recruitment and activation2020

    • Author(s)
      Mikito Shimizu, Tatsusada Okuno, Makoto Kinoshita, Hisae Sumi, Harutoshi Fujimura, Kazuya Yamashita, Tomoyuki Sugimoto, Shuhei Sakakibara, Kaori Sakakibara, Toru Koda, Satoru Tada, Teruyuki Ishikura, Hisashi Murata, Shohei Beppu, Naoyuki Shiraishi, Yasuko Sugiyama, Yuji Nakatsuji, Atsushi Kumanogoh & Hideki Mochizuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 13274-13274

    • DOI

      10.1038/s41598-020-70203-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sema4A is implicated in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase2020

    • Author(s)
      Koda Toru、Namba Akiko、Kinoshita Makoto、Nakatsuji Yuji、Sugimoto Tomoyuki、Sakakibara Kaori、Tada Satoru、Shimizu Mikito、Yamashita Kazuya、Takata Kazushiro、Ishikura Teruyuki、Murata Syo、Beppu Shohei、Kumanogoh Atsushi、Mochizuki Hideki、Okuno Tatsusada
    • Journal Title

      Journal of Neuroinflammation

      Volume: 17 Issue: 1 Pages: 1-9

    • DOI

      10.1186/s12974-020-01757-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single injection of sustained-release prostacyclin analog ONO-1301-MS ameliorates hypoxic toxicity in the murine model of amyotrophic lateral sclerosis.2019

    • Author(s)
      Tada S, Okuno T, Shimizu M, Sakai Y, Sumi-Akamaru H, Kinoshita M, Yamashita K, Sanda E, Choong CJ, Namba A, Sasaki T, Koda T, Takata K, Miyagawa S, Sawa Y, Nakatsuji Y, Mochizuki H.
    • Journal Title

      Sci Rep.

      Volume: 27 Issue: 1 Pages: 5252-5252

    • DOI

      10.1038/s41598-019-41771-4

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk of stroke early after implantation of a left ventricular assist device.2019

    • Author(s)
      Samura T, Yoshioka D, Toda K, Sakaniwa R, Shimizu M, Miyagawa S, Yoshikawa Y, Hata H, Saito S, Sakata Y, Sawa Y.
    • Journal Title

      J Thorac Cardiovasc Surg.

      Volume: 157 Pages: 259-267

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Beneficial effects of fingolimod in MS patients with high serum Sema4A levels2018

    • Author(s)
      Koda Toru、Namba Akiko、Nakatsuji Yuji、Niino Masaaki、Miyazaki Yusei、Sugimoto Tomoyuki、Kinoshita Makoto、Takata Kazushiro、Yamashita Kazuya、Shimizu Mikito、Fukazawa Toshiyuki、Kumanogoh Atsushi、Mochizuki Hideki、Okuno Tatsusada
    • Journal Title

      PLoS One

      Volume: 13 Issue: 3 Pages: 1-10

    • DOI

      10.1371/journal.pone.0193986

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebrospinal fluid mitochondrial DNA in neuromyelitis optica spectrum disorder2018

    • Author(s)
      Yamashita Kazuya、Kinoshita Makoto、Miyamoto Katsuichi、Namba Akiko、Shimizu Mikito、Koda Toru、Sugimoto Tomoyuki、Mori Yuki、Yoshioka Yoshichika、Nakatsuji Yuji、Kumanogoh Atsushi、Kusunoki Susumu、Mochizuki Hideki、Okuno Tatsusada
    • Journal Title

      Journal of Neuroinflammation

      Volume: 15 Issue: 1 Pages: 125-125

    • DOI

      10.1186/s12974-018-1162-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The analysis of the monocyte role in NMO with patient-derived AQP4 recombinant antibody2019

    • Author(s)
      清水 幹人
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 患者由来recombinant抗AQP4モノクローナル抗体を持ちいた NMO病態における自然免疫経路の解析2019

    • Author(s)
      清水 幹人
    • Organizer
      第31回日本神経免疫学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification of innate immunity activation in the pathogenesis of NMO2019

    • Author(s)
      清水 幹人
    • Organizer
      ECTRIMS 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Blood flow modulation therapy by prostacyclin agonist ameliorates ALS mice model2018

    • Author(s)
      Mikito Shimizu, Satoru Tada, Tatsusada Okuno, Yoshiki Sakai, Hisae Sumi, Makoto Kinoshita, Kazuya Yamashita, Eri Sanda, Choong Chi-Jing, Akiko Hosokawa-Namba, Tsutomu Sasaki, Toru Koda, Kazushiro Takata, Shigeru Miyagawa, Yoshiki Sawa, Yuji Nakatsuji, Hideki Mochizuki
    • Organizer
      神経内科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] リコンビナント抗AQP4抗体を用いたNMOの病態解析2018

    • Author(s)
      清水幹人, 木下允, 甲田亨, 南波明子, 山下和哉, 石倉照之, 中辻裕司, 熊ノ郷淳, 望月秀樹, 奥野龍禎
    • Organizer
      神経免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Intestinal succinic acid exacerbate experimental autoimmune encephalitis2018

    • Author(s)
      Mikito Shimizu, Kazushiro Takata, Makoto Kinoshita, Teruyuki Ishikura, Toru Koda, Tatsusada Okuno, Yuji Nakatsuji, Hideki Mochizuki
    • Organizer
      ECTRIMS
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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