Fakhoury Marc
Department of Neuroscience, Faculty of Medicine, University of Montreal, Montreal, Que., Canada.
Neurodegener Dis. 2015;15(2):63-9. doi: 10.1159/000369933. Epub 2015 Jan 15.
Neurodegenerative diseases are the result of progressive loss of neurons and axons in the central nervous system (CNS), which can lead to cognition and motor dysfunction. It is well known that CNS inflammation and immune activation play a major role in the pathophysiology of neurodegenerative diseases. Although the blood-brain barrier (BBB) is able to protect the CNS from immune activation, it becomes more permeable during inflammation, which renders the brain vulnerable to infections. A better understanding of the interaction between inflammatory mediators, such as cytokines, and the activated immune response, including astrocytes and microglia, is critical for the development of new therapeutic strategies for neurodegenerative diseases. This review first describes the role of innate immune activation in neurodegenerative diseases and illustrates the factors that contribute to the communication between the CNS and the immune system. A closer look is given at the role of the BBB in inflammation and immunity, as well as at the animal models used to study inflammation in neurodegenerative diseases. Finally, this review outlines the key pathways and biological mechanisms involved in CNS diseases, with a particular focus on multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD).
神经退行性疾病是中枢神经系统(CNS)中神经元和轴突逐渐丧失的结果,这可能导致认知和运动功能障碍。众所周知,中枢神经系统炎症和免疫激活在神经退行性疾病的病理生理学中起主要作用。尽管血脑屏障(BBB)能够保护中枢神经系统免受免疫激活,但在炎症期间它会变得更具渗透性,这使大脑易受感染。更好地理解炎症介质(如细胞因子)与包括星形胶质细胞和小胶质细胞在内的激活免疫反应之间的相互作用,对于开发神经退行性疾病的新治疗策略至关重要。本综述首先描述先天性免疫激活在神经退行性疾病中的作用,并阐述促成中枢神经系统与免疫系统之间通信的因素。更深入地探讨血脑屏障在炎症和免疫中的作用,以及用于研究神经退行性疾病炎症的动物模型。最后,本综述概述了中枢神经系统疾病所涉及的关键途径和生物学机制,特别关注多发性硬化症(MS)、帕金森病(PD)和阿尔茨海默病(AD)。