Elucidating the mechanism of myelination : FcRγ-Fyn-MBP stream is critical for the CNS myelination.
| Project/Area Number |
16300124
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare |
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Principal Investigator |
ASOU Hiroaki Tokyo metropolitan Institute of Gerontology, Subhead of a department, 東京都老人総合研究所, 研究副部長 (30104160)
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| Co-Investigator(Kenkyū-buntansha) |
SEIWA Chika Tokyo metropolitan Institute of Gerontology, Investigator, 東京都老人総合研究所, 研究員 (60399459)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | myelin / myelin basic protein / immunoglobulin Fc receptor / oligodendrocyte / myelinogenesis / mechanism of myelination / Remyelination / recepter ligand / オリゴデンドロサイト前駆細胞 / ミエリン新生 / 脳内リガンド |
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| Research Abstract |
Elucidation of the mechanism of CNS myelinogenesis is ultimately required to cure demyelinating disease. We have elucidated the mechanism whereby the γ chain of immunoglobulin Fc recepter(FcR γ ), an essential signaling molecule of the immune system, functions as a trigger for oligodendroglial myelinogenesis. FcR γ signaling results in the up-regulation of Fyn tyrosine kinase (Fyn) and myelin basic protein (MBP) expression levels, in addition to the morphological differentiation of oligodendroglia. Mice deficient in FcR γ demonstrate severely disturbed myelinogenesis, similar to the defect observed in mice deficient in either Fyn or MBP. FcR γ -Fyn double deficient mice exhibit severer hypomyelination and decrease in MBP than those of both single mutant mice, implying that FcR γ -Fyn-MBP cascade is indeed critical for the myelinogenesis. We have also detected expression of Fc recepters specific for immunoglobulin G in conjunction with FcR γ in oligodendroglia, suggesting immunogloblins may contribute to myelinogenesis. Expression of CD45, a regulator of Fyn, in oligodendroglia suggests the involvement of this molecule in the proposed mechanism. Our findings uncover a new connection between the brain and the immune system involved in myelinogenesis, introducing a novel therapeutic avenue leading to a possible cure for demyelinating disease.
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Report
(3 results)
Research Products
(17 results)
