斯芬戈-1-酸盐受体1调节器ponesimod修复了cuprizone诱导的脱髓化,并诱导了寡细胞分化
Emily Willems1,2, Melissa Schepers1,2,3, Elisabeth Piccart1
1Department of Neuroscience, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
概括
尼西莫德是一种基-1-酸盐受体1 (S1PR1) 调节剂,通过增强寡基细胞前体细胞分化,促进了转基因化,并在小鼠脱基因化模型中逆转认知缺陷.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 氨酸-1-酸受体 (S1PR) 调节剂通过防止淋巴细胞退出和神经炎症来治疗多发性硬化症 (MS).
- 新出现的证据表明,S1PR调制可能会促进复髓化.
- S1P1在寡头细胞前体细胞 (OPC) 中表达很高,这表明它在复髓化中发挥了直接作用.
研究的目的:
- 通过提高OPC差异化来研究西莫德对S1P1的功能抗是否会诱导复髓化.
- 评估ponesimod对功能恢复和髓化在cuprizone诱导的脱髓化小鼠模型中的影响.
主要方法:
- 在Cuprizone小鼠模型中,表现出脱髓化.
- 使用视觉唤起潜能 (VEP) 评估功能性复髓化.
- 使用Y迷宫测试对工作记忆的评估.
- 通过髓基蛋白 (MBP) 免疫组织化学和传输电子显微镜分析髓化.
- 使用O4免疫细胞化学进行OPC分化的体外评估.
主要成果:
- 波尼西莫德降低了VEP延迟,表明功能性复髓化.
- 波尼西莫德可以扭转cuprizone诱导的工作记忆缺陷.
- 随着ponesimod治疗,观察到大脑质体内髓化增加.
- 尼西莫德在体外显著增加了小鼠初级OPC分化,单独或与S1P5调节器一起.
结论:
- 通过ponesimod对S1P1的功能对抗在脱髓化模型中促进了复髓化.
- 西莫德增强了OPC的分化,这表明有直接的亲转基因化机制.
- 在神经系统疾病中,S1P1调制代表了促进髓修复的潜在治疗策略.
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