Mechanisms related to the pathogenesis of the optic neuritis and the development of new therapeutic avenues

视神经炎发病机制及新治疗途径的开发

• 批准号: 21791726
• 负责人: KAKU Gyourei
• 金额: $ 2.75万
• 依托单位: 財団法人東京都医学研究機構 (2010)Tokyo Metropolitan Organization for Medical Research (2009)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791726/
• 关键词: 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

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.

我们的研究使用实验性自身免疫性脑脊髓炎（EAE），一种多发性硬化症（MS）的动物模型来阐明视神经炎发病机制的可能机制。首先，我们研究了凋亡相关激酶 1 (ASK1) 缺陷对 EAE 严重程度的影响。我们的结果表明，ASK1 缺陷可减轻 EAE 中的神经炎症，而不影响 T 细胞的增殖能力。此外，口服特定的小分子量 ASK1 抑制剂可抑制 EAE 诱导的脊髓和视神经自身免疫炎症。这些结果表明 ASK1 可能作为包括 MS 在内的自身免疫性脱髓鞘疾病的有效治疗靶点。其次，我们发现olig1（一种对少突胶质细胞发育重要的基因）的缺陷延迟了EAE疾病的发病，这表明olig1信号通路可能与MS神经系统症状的发生率和严重程度有关。第三，我们发现口服亚精胺（我们饮食中的天然成分）可以减轻视神经炎的严重程度，这表明亚精胺可能适合治疗多发性硬化症和视神经炎。

项目成果

Glia-and neuron-specific functions of TrkB signaling during retinal degeneration and regeneration.

视网膜变性和再生过程中 TrkB 信号传导的神经胶质细胞和神经元特异性功能。

• 发表时间: 2011
• 作者: Harada C.; Guo X.; Namekata K.; Kimura A.; Nakamura K.; Tanaka K.; Parada L.F.; Harada T
• 通讯作者: Harada T

Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis.

香叶基香叶基丙酮对实验性自身免疫性脑脊髓炎视神经炎的影响。

• 发表时间: 2009
• 作者: Guo; X.
• 通讯作者: X.

Optic Nerve Regeneration is Enhanced in Dock3 Overexpressing Transgenic Mice.

Dock3 过表达转基因小鼠的视神经再生得到增强。

• 发表时间: 2011
• 作者: Namekata K.; Harada C.; Guo X.; Harada T
• 通讯作者: Harada T

Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex.

Dock3 通过刺激 WAVE 复合物的膜募集来诱导轴突生长。

• 发表时间: 2010
• 作者: Namekata; K.; et al.
• 通讯作者: et al.

Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex.

Dock3 通过刺激 WAVE 复合物的膜募集来诱导轴突生长。

• 作者: Namekata; K.
• 通讯作者: K.