Simard A R, Rivest S
Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, QC, Canada.
Mol Psychiatry. 2006 Apr;11(4):327-35. doi: 10.1038/sj.mp.4001809.
The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associated with more damages or less repair. We have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that derive from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These newly recruited cells are specifically attracted to the beta-amyloid 40/42 isoforms in vivo and they participate in the elimination of these proteins by phagocytosis. This review presents the mechanisms involved in the control of the innate immune response by microglia and the beneficial properties of such a response in brain diseases, such as AD.
先天性免疫和小胶质细胞在大脑中的作用目前是一个极具争议的问题。虽然多项研究提供了证据表明它们在各种脑部疾病和创伤的动物模型中会导致神经退行性变,但其他研究表明,抑制它们反而可能与更多损伤或更少修复相关。我们最近报道了存在两种不同类型的小胶质细胞,即驻留型小胶质细胞和源自骨髓干细胞的新分化小胶质细胞。非常有趣的是,血液来源的小胶质细胞与淀粉样斑块有关,并且这些细胞能够在出现阿尔茨海默病(AD)主要特征的小鼠中防止淀粉样沉积物的形成或消除其存在。这些新招募的细胞在体内被特异性吸引到β-淀粉样蛋白40/42异构体,并且它们通过吞噬作用参与这些蛋白质的清除。本综述介绍了小胶质细胞控制先天性免疫反应所涉及的机制以及这种反应在诸如AD等脑部疾病中的有益特性。