Fernandes Adelaide, Miller-Fleming Leonor, Pais Teresa F
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisbon, Portugal.
Cell Mol Life Sci. 2014 Oct;71(20):3969-85. doi: 10.1007/s00018-014-1670-8. Epub 2014 Jul 10.
Microglial cells contribute to normal function of the central nervous system (CNS). Besides playing a role in the innate immunity, they are also involved in neuronal plasticity and homeostasis of the CNS. While microglial cells get activated and undergo phenotypic changes in different disease contexts, they are far from being the "villains" in the CNS. Mounting evidence indicates that microglial dysfunction can exacerbate the pathogenesis of several diseases in the CNS. Several molecular mechanisms tightly regulate the production of inflammatory and toxic factors released by microglia. These mechanisms involve the interaction with other glial cells and neurons and the fine regulation of signaling and transcription activation pathways. The purpose of this review is to discuss microglia activation and to highlight the molecular pathways that can counteract the detrimental role of microglia in several neurologic diseases. Recent work presented in this review support that the understanding of microglial responses can pave the way to design new therapies for inflammatory diseases of the CNS.
小胶质细胞对中枢神经系统(CNS)的正常功能有贡献。除了在先天免疫中发挥作用外,它们还参与神经元可塑性和中枢神经系统的稳态。虽然小胶质细胞在不同疾病背景下会被激活并发生表型变化,但它们远非中枢神经系统中的“反派”。越来越多的证据表明,小胶质细胞功能障碍会加剧中枢神经系统中几种疾病的发病机制。几种分子机制严格调节小胶质细胞释放的炎症和毒性因子的产生。这些机制涉及与其他神经胶质细胞和神经元的相互作用以及信号传导和转录激活途径的精细调节。本综述的目的是讨论小胶质细胞的激活,并强调可以抵消小胶质细胞在几种神经系统疾病中有害作用的分子途径。本综述中展示的最新研究成果支持,对小胶质细胞反应的理解可为设计中枢神经系统炎症性疾病的新疗法铺平道路。