A trial of amyotrophic lateral sclerosis (ALS) therapy targeting on semanhorins

针对 Semanhorins 的肌萎缩侧索硬化症 (ALS) 治疗试验

• 批准号: 20790611
• 负责人: OKUNO Tatsusada
• 金额: $ 2.66万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790611/
• 关键词: 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

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.

Sema4D/CD100是一种IV类信号素，已被证明分别通过其受体Plexin-B1和CD72参与神经系统和免疫系统的调节。然而，Sema4D在神经炎症中的作用仍不清楚。我们在这里发现，Sema4D促进了原代小鼠小胶质细胞诱导型一氧化氮合酶(INOS)的表达，这种作用在丛状蛋白-B1中被取消，但在CD72缺陷的小胶质细胞中不被取消。此外，在实验性自身免疫性脑脊髓炎(EAE)的发展过程中，我们观察到Sema4D和Plexin-B1分别在浸润性单个核细胞和小胶质细胞中诱导表达。与这些表达谱相一致的是，将来自野生型小鼠的生脑T细胞过继转移到Plexin-Bl缺陷小鼠或带有Plexin-Bl缺陷CNS驻留细胞的骨髓嵌合体小鼠中，EAE的发展明显减弱。此外，阻断针对Sema4D的抗体显著抑制了EAE发展过程中的神经炎症。总之，我们的发现不仅证明了Sema4D-Plexin-B1相互作用在小胶质细胞激活中的作用，而且还提供了它们在神经炎症中的病理意义。

项目成果

A midline switch of receptor processing regulates commissural axon guidance in vertebrates

• DOI: 10.1101/gad.542510
• 发表时间: 2010-02-15
• 期刊: GENES & DEVELOPMENT
• 影响因子: 10.5
• 作者: Nawabi, Homaira;Briancon-Marjollet, Anne;Castellani, Valerie
• 通讯作者: Castellani, Valerie

Involvement of Sema4A in the progression of experimental autoimmune myocarditis

• DOI: 10.1016/j.febslet.2008.10.040
• 发表时间: 2008-11-26
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Makino, Nobuhiko;Toyofuku, Toshihiko;Kumanogoh, Atsushi
• 通讯作者: Kumanogoh, Atsushi

Neuromyelitis optica: Passive transfer to rats by human immunoglobulin

• DOI: 10.1016/j.bbrc.2009.06.085
• 发表时间: 2009-09-04
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Kinoshita, Makoto;Nakatsuji, Yuji;Sakoda, Saburo
• 通讯作者: Sakoda, Saburo

多発性硬化症の発症とSema4D臨床免疫

多发性硬化症的发展和 Sema4D 临床免疫

• 发表时间: 2010
• 期刊: アレルギー科 53(5)
• 作者: 奥野龍禎;熊ノ郷淳
• 通讯作者: 熊ノ郷淳

Edaravone, a free radical scavenger, ameliorates experimental autoirnmune encephalomyelitis

自由基清除剂依达拉奉可改善实验性自身免疫性脑脊髓炎

• 发表时间: 2008
• 期刊: Neuroscience letter 440
• 作者: Moriya M;Nakatsuji Y;Miyamoto K;Okuno T;Kinoshita M;Kumanogoh A;Kusunoki S;Sakoda S
• 通讯作者: Sakoda S