感染和慢性疾病会激活一个全身大脑肌肉信号轴
Shuo Yang1,2, Meijie Tian3, Yulong Dai4,5,6
1Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Science immunology
|July 12, 2024
概括
感染或疾病引起的神经炎症导致大脑反应性氧物种 (ROS). 这会触发大脑到肌肉的信号,导致肌肉功能障碍和运动功能受损,这表明IL-6是治疗目标.
科学领域:
- 神经免疫学 神经免疫学
- 分子生物学分子生物学
- 肌肉生理学 肌肉生理学
背景情况:
- 由感染和神经退行性疾病引发的神经炎症,与肌肉疼痛和疲劳等非神经症状有关.
- 中枢神经系统 (CNS) 炎症影响外围组织,特别是肌肉的机制尚不清楚.
研究的目的:
- 研究将中枢神经系统压力因素与系统性病理,特别是肌肉功能障碍联系起来的分子通路.
- 确定潜在的治疗点,以减轻与疾病相关的肌肉虚弱.
主要方法:
- 开发了Drosophila和小鼠模型模拟感染 (大肠杆菌) 和神经退行性疾病 (粉样β表达).
- 测量了大脑中的活性氧物种 (ROS),细胞因子表达 (Upd3 / IL-6) 和骨肌肉中的JAK-STAT通路激活.
- 评估运动功能和肌肉线粒体健康.
主要成果:
- 中枢神经系统的压力因素 (感染,SARS-CoV-2蛋白,Aβ42) 诱导了大脑ROS的积累.
- 大脑ROS上调了Upd3/IL-6,从而激活了骨肌肉中的JAK-STAT通路.
- 这种系统信号轴导致肌肉线粒体功能障碍和运动功能受损.
结论:
- 一个新的脑肌信号轴存在,其中中枢神经系统衍生的细胞因子在感染和慢性疾病期间调解系统效应.
- 介质素-6 (IL-6) 被确定为这个轴的关键调解者,也是肌肉功能障碍的潜在治疗标.
- 了解这种途径可以了解与神经疾病相关的非神经症状.
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