人类免疫缺陷病毒1 糖蛋白120 诱导神经元内细胞网膜应激
Christy Agbey1,2, Lee A Campbell2, Thieu Phan3
1Interdisciplinary Program in Neuroscience, Washington, DC, USA.
Cell death & disease
|October 6, 2025
概括
艾滋病毒相关的神经认知障碍 (HAND) 可能发生尽管治疗. 这项研究表明,艾滋病毒蛋白 gp120 引起神经元内质网膜 (ER) 压力,导致神经毒性和 HAND 病原体.
科学领域:
- 神经科学是一个神经科学.
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 与艾滋病毒相关的神经认知障碍 (HAND) 仍然是艾滋病毒感染者 (PLWH) 面临的挑战,尽管有抗逆转录病毒治疗.
- 艾滋病毒包膜蛋白gp120与HAND特征的神经元损伤有关.
- 了解gp120的神经毒性机制对于开发新疗法至关重要.
研究的目的:
- 为了研究HIV gp120对脑内质网膜 (ER) 动态和神经元功能的影响.
- 为了确定gp120诱导的ER变化是否有助于与HAND相关的神经毒性.
主要方法:
- 在gp120转基因小鼠和培养神经元中,对ER压力标志物 (BiP,p-IRE1α) 的西部斑分析.
- 电子显微镜用于评估gp120tg小鼠和神经元培养中的ER形态.
- 化基因受体对抗剂 (AMD3100) 测试受体依赖性.
- 使用记者蛋白 (Gluc-ASARTDL) 进行Ca2+活体成像,以监测ER水平.
主要成果:
- gp120转基因小鼠表现出增加的BiP和p-IRE1α水平,并在海马体中改变了ER形态.
- gp120暴露改变了培养的老鼠皮层神经元中的ER形态.
- gp120的影响取决于CXCR4共受体,因为AMD3100阻止了gp120对BiP的影响.
- gp120诱导神经元中的ER耗尽.
结论:
- 艾滋病毒蛋白 gp120 诱导神经元内质网膜压力.
- 由gp120介导的ER压力,以耗和形态改变为特征,是HIV神经毒性和HAND的潜在机制.
- 针对ER压力路径可能为HAND提供新的治疗策略.
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