通过Src-PLCγ-calpain通路的缺血后,IL-17A会加剧卡斯巴-12-依赖的神经元亡
Hongyu Wang1, Song Han1, Jinjin Xie1
1Department of Neurobiology, School of Basic Medical Science, Capital Medical University, Beijing 100069, PR China.
Experimental neurology
|June 13, 2024
概括
介质蛋白-17A (IL-17A) 通过激活caspase-12来促进中风后的神经元死亡. 阻断IL-17A在中风模型中减少了脑损伤和神经元亡,表明了治疗潜力.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 干白素-17A (IL-17A) 与中风患者的炎症和二次损伤有关.
- 缺血性神经元死亡中IL-17A的确切机制尚不清楚.
研究的目的:
- 为了研究IL-17A在促进神经元亡的作用,在缺血性中风.
- 为了阐明参与IL-17A介导的神经元死亡的分子途径.
主要方法:
- 对于缺血性中风中脑动脉封闭/再输 (MCAO/R) 的小鼠模型.
- 氧气-葡萄糖剥夺/重新氧化 (OGD/R) 以模拟神经元中的体外缺血.
- 使用IL-17A中和单克隆抗体 (mAb) 和calpain和脂酶Cγ (PLCγ) 的抑制剂.
主要成果:
- 一个通过caspase-12通路加速的内等质网膜应激 (ERS) 诱导的神经元亡.
- 阻断calpain或PLCγ通过防止caspase-12裂变来抑制IL-17A介导的亡.
- IL-17A与Src和PLCγ相互作用,导致Ca2+流动和calpain-caspase-12级联的激活.
- 在MCAO小鼠中,中和mAb的IL-17A的脑内静脉注射减少了脑损伤和亡.
结论:
- 在缺血性中风中,IL-17A通过caspase-12激活加剧神经元亡.
- 向IL-17A可能为缺血性中风治疗提供一种潜在的治疗策略.
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