Ashford B A, Boche D, Cooper-Knock J, Heath P R, Simpson J E, Highley J R
University of Sheffield, Sheffield, UK.
University of Southampton, Southampton, UK.
Neuropathol Appl Neurobiol. 2021 Feb;47(2):179-197. doi: 10.1111/nan.12640. Epub 2020 Jul 21.
Motor Neuron Disease (MND) is a fatal neurodegenerative condition, which is characterized by the selective loss of the upper and lower motor neurons. At the sites of motor neuron injury, accumulation of activated microglia, the primary immune cells of the central nervous system, is commonly observed in both human post mortem studies and animal models of MND. Microglial activation has been found to correlate with many clinical features and importantly, the speed of disease progression in humans. Both anti-inflammatory and pro-inflammatory microglial responses have been shown to influence disease progression in humans and models of MND. As such, microglia could both contribute to and protect against inflammatory mechanisms of pathogenesis in MND. While murine models have characterized the microglial response to MND, these studies have painted a complex and often contradictory picture, indicating a need for further characterization in humans. This review examines the potential role microglia play in MND in human and animal studies. Both the pro-inflammatory and anti-inflammatory responses will be addressed, throughout the course of disease, followed by the potential of microglia as a target in the development of disease-modifying treatments for MND.
运动神经元病（MND）是一种致命的神经退行性疾病，其特征是上下运动神经元选择性丧失。在运动神经元损伤部位，中枢神经系统的主要免疫细胞——活化小胶质细胞的积累，在人类尸检研究和MND动物模型中均普遍观察到。已发现小胶质细胞活化与许多临床特征相关，重要的是，与人类疾病进展速度相关。抗炎和促炎小胶质细胞反应均已显示会影响人类和MND模型中的疾病进展。因此，小胶质细胞既可能促成MND发病机制的炎症过程，也可能起到保护作用。虽然小鼠模型已对小胶质细胞对MND的反应进行了表征，但这些研究描绘了一幅复杂且往往相互矛盾的图景，表明需要在人类中进行进一步表征。本综述探讨了小胶质细胞在人类和动物研究中在MND中所起的潜在作用。将阐述疾病过程中促炎和抗炎反应，随后探讨小胶质细胞作为MND疾病修饰治疗开发靶点的潜力。
