A trial of amyotrophic lateral sclerosis (ALS) therapy targeting on semanhorins
| Project/Area Number |
20790611
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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 |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
OKUNO Tatsusada Osaka University, 微生物学研究所, 助教 (00464248)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 筋萎縮性側索硬化症 / Sema4D / 運動ニューロン保護 / ミクログリア / EAE / セマフォリン / neuroinflammation / 実験的自己免疫性脳脊髄炎 / iNOS / プレキシン / CD100 / 運動神経保護 |
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| Research Abstract |
Sema4D/CD100, a class IV semaphorin, has been shown to be involved in the nervous and immune systems through its receptors Plexin-Bl and CD72, respectively. However, the involvement of Sema4D in neuroinflammation still remains unclear. We here found that Sema4D promoted inducible nitric oxide synthase (iNOS)-expression by primary mouse microglia, of which effects were abolished in Plexin-B1- but not in CD72-deficient microglia. In addition, during the development of experimental autoimmune encephalomyelitis (EAE), we observed that the expression of Sema4D and Plexin-B1 was induced in infiltrating mononuclear cells and microglia, respectively. Consistent with these expression profiles, when encephalitogenic T-cells derived from wild-type mice were adoptively transferred into Plexin-Bl-deficient mice or bone marrow chimera mice with Plexin-Bl-deficient CNS-resident cells, the development of EAE was considerably attenuated. Furthermore, blocking antibodies against Sema4D significantly inhibited neuroinflammation during EAE-development. Collectively, our findings not only demonstrate the role of Sema4D-Plexin-B1 interactions in the activation of microglia but also provide their pathological significance in neuroinflammation.
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Kumanogoh A Roles of Sema4D-Plexin-B1 Interactions in the Central Nervous System for Pathogenesis of Experimental Autoimmune Encephalomyelitis2010
Author(s)
Okuno T, Nakatsuji Y, Moriya M, Takamatsu H, Nojima S, Takegahara N, Toyofuku T, Nakagawa Y, Kang S, Friedel RH, Sakoda S, Kikutani H
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Journal Title
Journal of Immunology 184(3)
Pages: 1499-506
Related Report
Peer Reviewed
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[Journal Article] A midline switch of receptor processing regulates commissural axon guidance in vertebrates2010
Author(s)
Nawabi H, Briancon-Marjollet1 A, Clark C, Sanyas I, Takamatsu H, Okuno T Kumanogoh A, Bozon1 M, Takeshima K, Yoshida Y, Moret F, Abouzid1 K, Castellani V
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Journal Title
Genes & Development 24(4)
Pages: 396-410
Related Report
Peer Reviewed
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[Journal Article] Roles of Sema4D-Plexin-B1 Interactions in the Central Nervous System for Pathogenesis of Experimental Autoimmune Encephalomyelitis.2010
Author(s)
Okuno T, Nakatsuji Y, Moriya M, Takamatsu H, Nojima S, Takegahara N, Toyofuku T, Nakagawa Y, Kang S, Friedel RH, Sakoda S, Kikutani H, Kumanogoh A
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Journal Title
Journal of Immunology 184(3)
Pages: 1499-1506
Related Report
Peer Reviewed
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[Journal Article] A midline switch of receptor processing regulates commissural axon guidance in vertebrates.2010
Author(s)
Nawabi H, Briancon-Marjolletl A, Clark C, Sanyas I, Takamatsu H, Okuno T, Kumanogoh A, Bozonl M, Takeshima K, Yoshida Y, Moret F, Abouzidl K, Castellani V
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Journal Title
Genes & Development 15;24(4)
Pages: 396-410
Related Report
Peer Reviewed
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[Journal Article]2008
Author(s)
Makino N, Toyofuku T, Takegahara N, Takamatsu H, Okuno T, Nakagawa Y, Kang S, Nojima S, Hori M, Kikutani H, Kumanogoh A.
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Journal Title
FEBS Left. 582(28)
Pages: 3935-40
Related Report
Peer Reviewed
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