小胶质细胞
神经退行性变
肌萎缩侧索硬化
神经科学
促炎细胞因子
神经炎症
生物
外围设备
炎症
免疫学
医学
病理
疾病
内科学
作者
Aude Chiot,Sakina Zaïdi,Charlène Iltis,M Ribon,Félix Berriat,Lorenzo Schiaffino,Ariane Jolly,Pierre de la Grange,Michel Mallat,Delphine Bohl,Stéphanie Millecamps,Danielle Seilhean,Christian S. Lobsiger,Séverine Boillée
标识
DOI:10.1038/s41593-020-00718-z
摘要
Microglia and peripheral macrophages have both been implicated in amyotrophic lateral sclerosis (ALS), although their respective roles have yet to be determined. We now show that macrophages along peripheral motor neuron axons in mouse models and patients with ALS react to neurodegeneration. In ALS mice, peripheral myeloid cell infiltration into the spinal cord was limited and depended on disease duration. Targeted gene modulation of the reactive oxygen species pathway in peripheral myeloid cells of ALS mice, using cell replacement, reduced both peripheral macrophage and microglial activation, delayed symptoms and increased survival. Transcriptomics revealed that sciatic nerve macrophages and microglia reacted differently to neurodegeneration, with abrupt temporal changes in macrophages and progressive, unidirectional activation in microglia. Modifying peripheral macrophages suppressed proinflammatory microglial responses, with a shift toward neuronal support. Thus, modifying macrophages at the periphery has the capacity to influence disease progression and may be of therapeutic value for ALS.
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