Involvement of ER stress-mediated MBP expression in myelin abnormalities in multiple sclerosis
| Project/Area Number |
17K07087
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Akita University (2018-2019)
Asahikawa Medical College (2017) |
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Principal Investigator |
BANDO YOSHIO 秋田大学, 医学系研究科, 教授 (20344575)
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| Co-Investigator(Kenkyū-buntansha) |
吉田 成孝 旭川医科大学, 医学部, 教授 (20230740)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ERストレス / オリゴデンドロサイト / 脱髄 / 髄鞘構造 / MBP / 小胞体ストレス / 自己抗体 / 多発性硬化症 |
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| Outline of Final Research Achievements |
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS, resulting in neurological impairments. However, the mechanism of relapsing has not been fully understood. On the other hand, we have recently found the possibility that demyelination with abnormal myelin morphology is involved in the pathogenesis of relapsing. In this project, we tried to understand the mechanism of abnormal myelin formation.
Abnormal myelin formation was induced by experimental autoimmune encephalomyelitis (EAE). In addition, anti-MOG autoantibody and ER-stress could induce this abnormality in the cultured oligodendrocytes. Moreover, we found that one of MBP isoform was significantly induced, but degenerated by these stresses, resulting in losing balance of MBP isoforms. By contrast, an ER chaperone inducer improved this phenomenon by refolding MBP protein. The ER chaperone inducer also suppressed progression of EAE and improved abnormal myelin formation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、自己抗体や炎症反応によって惹起されるERストレスによりOLにおけるMBPの蛋白合成が異常となった結果、産生される変性MBPが異常な髄鞘構造の形成に関与していることを明らかにした。さらに、分子シャペロン誘導剤を用いることによってこのような異常な髄鞘構造の形成を抑制でき、EAEの症状を改善できることも明らかにした。これら一連の成果はERストレスを標的とした薬剤がMS治療に有効である可能性を示唆するものであり、これまでにない全く新しい視点のMS治療薬を開発する上で基盤になるものと思われ、社会的にも貢献するものであると考えられる。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Kallikrein 6 secreted by oligodendrocytes regulates the progression of experimental autoimmune encephalomyelitis2018
Author(s)
Bando Y, Hagiwara Y, Suzuki Y, Yoshida K, Aburakawa Y, Kimura T, Murakami C, Ono M, Tanaka T, Jiang Y-P, Mitrovi B, Bochimoto H, Yahara O, Yoshida S
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Journal Title
Glia
Volume: 66
Pages: 359-378
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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