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小胶质细胞是中枢神经系统内的内源性免疫细胞,在中枢神经系统的固有免疫反应中扮演关键的角色,其主要作用是早期控制感染及激活适应性免疫系统细胞,以清除病原体。小胶质细胞引发的固有和适应性免疫反应包括前炎性因子的释放。虽然有效的免疫反应对于防御病原体的侵害是必须的,但中枢神经系统的炎症反应也会造成相应的组织损伤和神经退行性变化。Toll样受体是模式识别受体家族中一个主要成员,不仅介导固有免疫反应,也参与适应性免疫反应。通过Toll样受体,小胶质细胞能识别中枢神经系统内的病原体配体及宿主配体。虽然越来越多的证据表明Toll样受体信号通路调节中枢神经系统有益的保护反应,但其诱导的小胶质细胞活化及前炎症因子释放也介导多种中枢神经系统疾病病理过程中的神经毒性作用。因此,Toll样受体介导的小胶质细胞活化对中枢神经系统的最终作用,取决于二者之间微妙的平衡。本文主要评述中枢神经系统内Toll样受体信号通路调控的神经退行性作用。
Microglia are endogenous immune cells within the central nervous system and play a key role in the innate immune response of the central nervous system. Their primary role is to control infection early and to activate adaptive immune system cells to clear pathogens. Innate and adaptive immune responses elicited by microglia include the release of pro-inflammatory cytokines. Although effective immune response is essential for defense against pathogens, the inflammation of the central nervous system can also cause corresponding tissue damage and neurodegenerative changes. Toll-like receptors, a key member of the pattern recognition receptor family, mediate both innate and adaptive immune responses. Through Toll-like receptors, microglial cells recognize pathogenic and host ligands in the central nervous system. Although there is increasing evidence that the Toll-like receptor signaling regulates a beneficial protective response in the central nervous system, its induction of microglial activation and the release of proinflammatory cytokines also mediate various pathological processes of central nervous system disease Neurotoxicity. Therefore, Toll-like receptor-mediated microglial activation of the central nervous system of the final effect, depending on the delicate balance between the two. This review focuses on the neurodegenerative effects of Toll-like receptor signaling in the central nervous system.