甲基氨酸受体8通过减轻内分泌网膜应激和线粒体功能障碍来抑制微质中的M1极化
Yangzhi Xie1, Liang Chen1, Jiacheng Chen2
1Department of Neurology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
Journal of integrative neuroscience
|February 29, 2024
概括
甲基氨酸受体8 (GRM8) 激活通过降低内分泌网膜 (ER) 应激和恢复线粒体功能来减少神经炎症. 这表明GRM8是神经退行性疾病的潜在治疗点.
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:
- 微质驱动的神经炎症是神经退行症的核心.
- 甲基氨酸受体8 (GRM8) 支持神经元的存活,但其在神经炎症中的作用尚不清楚.
- 由过载引起的内质网膜 (ER) 压力和线粒体功能障碍会引发神经炎症.
研究的目的:
- 研究GRM8在微质中的抗炎作用.
- 确定GRM8在缓解ER压力和线粒体功能障碍方面的作用.
- 探索GRM8对信号通路的影响.
主要方法:
- 在暴露于脂多糖糖之前,BV2微质细胞被用GRM8激动剂治疗.
- 评估了促炎性细胞因子,微质两极分化和神经元活力.
- 量化cAMP,依赖伊诺西-1,4,5-三酸盐受体 (IP3R) 的释放,ER,线粒体功能,ER压力标志物和NF-κB激活.
主要成果:
- GRM8激活抑制了促炎性细胞因子,并促进了抗炎性微质表型.
- GRM8增强了共培养的神经元类PC12细胞的存活率.
- GRM8抑制了cAMP,使IP3R无敏,减少了释放,恢复了线粒体功能,减轻了ER压力,并关闭了NF-κB信号传递.
结论:
- GRM8激活通过减少ER压力和线粒体功能障碍来保护神经炎症.
- IP3R介导的信号对GRM8的保护作用至关重要.
- GRM8代表了神经炎症的一个有前途的治疗点.
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