Mechanisms related to the pathogenesis of the optic neuritis and the development of new therapeutic avenues
| Project/Area Number |
21791726
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | 財団法人東京都医学研究機構 (2010)
Tokyo Metropolitan Organization for Medical Research (2009) |
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Principal Investigator |
KAKU Gyourei 財団法人東京都医学研究機構, 東京都神経科学総合研究所, 研究員 (50443114)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 多発性硬化症 / 視神経炎 / グリア自然免疫 / 抗酸化物質 / グリア / EAE |
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| Research Abstract |
Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), was used in our study to elucidate the possible mechanisms underlying the pathogenesis of the optic neuritis. Firstly, we investigated the effect of apoptosis-related kinase 1 (ASK1) deficiency on the severity of EAE. Our results show that ASK1 deficiency attenuates neuroinflammation in EAE, without affecting the proliferation capability of T cells. Moreover, oral treatment with a specific small molecular weight inhibitor of ASK1 suppressed EAE-induced autoimmune inflammation in both spinal cords and optic nerves. These results suggest that ASK1 may serve as a valid therapeutic target for autoimmune demyelinating disorders including MS. Secondly, we found that the deficiency of olig1, a gene important for the development of oligodendrocytes, delayed the onset of EAE disease, suggesting that the olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS. Thirdly, we found that oral administration of spermidine, a natural component of our diet, reduced the severity of the optic neuritis, suggesting that spermidine might be suitable for the treatment of MS and optic neuritis.
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Report
(3 results)
Research Products
(33 results)
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[Journal Article] Regulation of the severity of neuroinflammation and demyelination by TLR-ASK1-p38 pathway.2010
Author(s)
Guo X., Harada C., Namekata K., Matsuzawa A., Camps M., Ji H., Swinnen D., Jorand-Lebrun C., Muzerelle M., Vitte P., Ruckle T., Kimura A., Kohyama K., Matsumoto Y., Ichijo H., Harada T
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Journal Title
EMBO Molecular Medicine 2
Pages: 504-515
Related Report
Peer Reviewed
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[Journal Article] Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in EAAC1-deficient mice.2009
Author(s)
Namekata K., Harada C., Guo X., Kikushima K., Kimura A., Fuse A., Mitamura Y., Kohyama K., Matsumoto Y., Tanaka K., Harada T
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Journal Title
Neuroscience Letter 465
Pages: 160-164
Related Report
Peer Reviewed
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