Analysis of microglial gene expression: identifying targets for CNS neurodegenerative and autoimmune disease.
Analysis of microglial gene expression: identifying targets for CNS neurodegenerative and autoimmune disease.
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DOI：
10.2165/00129785-200404050-00005
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Lo, David
中科院分区：
文献类型：
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作者：
Carson, Monica J;Thrash, J Cameron;Lo, David
小胶质细胞是中枢神经系统（CNS）的组织巨噬细胞，其激活是中枢神经系统功能障碍和疾病的最早迹象之一。由于小胶质细胞表达许多巨噬细胞标记物，它们被认为主要作为中枢神经系统炎症和破坏的效应器。虽然这些反应在一定程度上是有益的，因为它们破坏了中枢神经系统病原体，但这些反应确实有可能产生神经毒性结果。因此，许多中枢神经系统退行性和炎症性疾病的治疗都是针对抑制小胶质细胞功能的。有证据表明，小胶质细胞在中枢神经系统的发育和中枢神经系统功能的维持中发挥着重要作用，可能不仅仅是防御病原体。小胶质细胞表型和功能的分子分析揭示了三个惊人的发现：(i)小胶质细胞是一种独特的中枢系统特异性组织巨噬细胞；（ii）它们在健康的中枢神经系统内是高度异质的；（iii）小胶质细胞的反应是针对中枢神经系统的特定区域和特定的病理损伤而精心定制的。我们认为，无处不在的小胶质细胞功能抑制（而不是靶向操作）可能无法完全改善中枢神经系统病理，甚至可能最终导致适应不良的结果。
Microglia are the tissue macrophage of the central nervous system (CNS) and their activation is among the earliest signs of CNS dysfunction and disease. Because microglia express many macrophage markers, they are presumed to act primarily as effectors of CNS inflammation and destruction. While such responses are beneficial to the extent that they destroy CNS pathogens, these responses do have the potential to have neurotoxic outcomes. Consequently, therapies for many CNS neurodegenerative and inflammatory diseases have been directed at suppressing microglial function. There is evidence to suggest that microglia play an important role during CNS development and maintenance of CNS function that may go beyond simple defense against pathogens. Molecular analysis of microglial phenotypes and function has revealed three striking findings: (i) that microglia are a unique CNS-specific type of tissue macrophage; (ii) that they are highly heterogeneous within the healthy CNS; and (iii) that microglial responses are exquisitely tailored to specific regions of the CNS and specific pathological insults. We suggest that ubiquitous suppression (rather than targeted manipulation) of microglial function may fail to fully ameliorate CNS pathology and may even ultimately promote maladaptive outcomes.