Attempt to improve multiple sclerosis progression by the control of intestinal mitochondrial oxidative stress
Project/Area Number |
18K15452
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52020:Neurology-related
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Research Institution | Osaka University |
Principal Investigator |
Shimizu Mikito 大阪大学, 医学系研究科, 招へい教員 (30817507)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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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)
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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.
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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。
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Report
(4 results)
Research Products
(12 results)
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[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
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 13274-13274
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Sci Rep.
Volume: 27
Issue: 1
Pages: 5252-5252
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
J Thorac Cardiovasc Surg.
Volume: 157
Pages: 259-267
Related Report
Peer Reviewed / Open Access
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[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
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