Chitnis Tanuja, Weiner Howard L
J Clin Invest. 2017 Oct 2;127(10):3577-3587. doi: 10.1172/JCI90609. Epub 2017 Sep 5.
There is an increasing recognition that inflammation plays a critical role in neurodegenerative diseases of the CNS, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and the prototypic neuroinflammatory disease multiple sclerosis (MS). Differential immune responses involving the adaptive versus the innate immune system are observed at various stages of neurodegenerative diseases, and may not only drive disease processes but could serve as therapeutic targets. Ongoing investigations into the specific inflammatory mechanisms that play roles in disease causation and progression have revealed lessons about inflammation-driven neurodegeneration that can be applied to other neurodegenerative diseases. An increasing number of immunotherapeutic strategies that have been successful in MS are now being applied to other neurodegenerative diseases. Some approaches suppress CNS immune mechanisms, while others harness the immune system to clear deleterious products and cells. This Review focuses on the mechanisms by which inflammation, mediated either by the peripheral immune response or by endogenous CNS immune mechanisms, can affect CNS neurodegeneration.
人们越来越认识到,炎症在中枢神经系统的神经退行性疾病中起着关键作用,这些疾病包括阿尔茨海默病、肌萎缩侧索硬化症、帕金森病以及典型的神经炎症性疾病多发性硬化症(MS)。在神经退行性疾病的各个阶段都观察到涉及适应性免疫系统与先天性免疫系统的不同免疫反应,这些反应不仅可能推动疾病进程,还可能成为治疗靶点。对在疾病病因和进展中起作用的特定炎症机制的持续研究揭示了有关炎症驱动的神经退行性变的经验教训,这些经验教训可应用于其他神经退行性疾病。越来越多在MS中取得成功的免疫治疗策略现在正应用于其他神经退行性疾病。一些方法抑制中枢神经系统免疫机制,而另一些方法则利用免疫系统清除有害产物和细胞。本综述重点关注由外周免疫反应或内源性中枢神经系统免疫机制介导的炎症影响中枢神经系统神经退行性变的机制。