Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2020 Dec 2;21(23):9188. doi: 10.3390/ijms21239188.
Over the past decade, research has unveiled the intimate relationship between neuroinflammation and neurodegeneration. Microglia and astrocytes react to brain insult by setting up a multimodal inflammatory state and act as the primary defenders and executioners of neuroinflammatory structural and functional changes. Microglia and astrocytes also play critical roles in the maintenance of normal brain function. This intricate balance of homeostatic and neuroinflammatory functions can influence the onset and the course of neurodegenerative diseases. The emergent role of the microglial-astrocytic axis in neurodegenerative disease presents many druggable targets that may have broad therapeutic benefits across neurodegenerative disease. Here, we provide a brief review of the basal function of both microglia and astrocytes, how they are changed in disease states, the significant differences between mouse and human glia, and use of human induced pluripotent stem cells derived from patients to study cell autonomous changes in human astrocytes and microglia.
在过去的十年中,研究揭示了神经炎症和神经退行性变之间的密切关系。小胶质细胞和星形胶质细胞通过建立多模态炎症状态对脑损伤作出反应,充当神经炎症结构和功能变化的主要防御者和执行者。小胶质细胞和星形胶质细胞在维持正常大脑功能方面也起着关键作用。这种内稳态和神经炎症功能的复杂平衡会影响神经退行性疾病的发病和病程。小胶质细胞-星形胶质细胞轴在神经退行性疾病中的新作用提出了许多可用药的靶点,这些靶点可能对神经退行性疾病具有广泛的治疗益处。在这里,我们简要回顾了小胶质细胞和星形胶质细胞的基本功能,它们在疾病状态下如何变化,以及小鼠和人类神经胶质细胞之间的显著差异,并利用患者来源的诱导多能干细胞来研究人类星形胶质细胞和小胶质细胞的自主细胞变化。