Bonifati Domenico Marco, Kishore Uday
Second Clinic of Neurology, Department of Neuroscience, University of Padua, Via Facciolati 51, Padova, Italy.
Mol Immunol. 2007 Feb;44(5):999-1010. doi: 10.1016/j.molimm.2006.03.007. Epub 2006 May 15.
The complement system provides an innate defence mechanism against pathogenic microorganisms. Although viewed for many years as an immune-privileged organ, the central nervous system contains many components of the immune system, including components of the complement system that are synthesized by astrocytes, microglia, and neurons. During the past two decades, a wide range of inflammatory markers, typically absent in the normal elderly population, have been reported in Alzheimer's disease brains. It is becoming evident that sustained brain inflammation might be an essential cofactor in Alzheimer disease and other neurodegenerative disorders such as Parkinson disease, dementia with Lewy bodies, Huntington's and prion diseases. The complement system may be useful in eliminating aggregated and toxic proteins associated with these neurological disorders and thus have a protective effect. However, an exaggerated or insufficient activation of the complement system can have deleterious effect through the activation of microglia, secretion of many proinflammatory cytokines, and generation of oxidative products. The role of complement-mediated inflammation in Alzheimer disease has drawn greater attention recently in view of new therapeutic advances made in the management of the disease. This review is meant to update the role of complement in Alzheimer's disease and other neurodegenerative disorders in view of recent vaccination and immunotherapeutic approaches.
补体系统为抵御病原微生物提供了一种先天性防御机制。尽管多年来中枢神经系统被视为免疫特权器官，但它包含许多免疫系统的成分，包括由星形胶质细胞、小胶质细胞和神经元合成的补体系统成分。在过去二十年中，阿尔茨海默病患者的大脑中出现了多种在正常老年人群中通常不存在的炎症标志物。越来越明显的是，持续的脑部炎症可能是阿尔茨海默病以及其他神经退行性疾病（如帕金森病、路易体痴呆、亨廷顿病和朊病毒病）的一个重要辅助因素。补体系统可能有助于清除与这些神经疾病相关的聚集性和毒性蛋白，从而起到保护作用。然而，补体系统的过度激活或激活不足可能会通过激活小胶质细胞、分泌多种促炎细胞因子以及产生氧化产物而产生有害影响。鉴于在该疾病管理方面取得的新治疗进展，补体介导的炎症在阿尔茨海默病中的作用最近受到了更多关注。鉴于最近的疫苗接种和免疫治疗方法，本综述旨在更新补体在阿尔茨海默病和其他神经退行性疾病中的作用。
