Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron loss and gliosis in the spinal cord, brain stem and cortex. The Notch signaling pathway has been reported to be dysfunctional in neurodegenerative diseases, including ALS. However, the exact mechanism is still unclear. Here, we detected Notch signaling activation in proliferating glial cells, Notch inactivation in motor neurons in the spinal cord of the SOD1-G93A model, and dramatic changes of cellular relocalization of Notch pathway signaling molecules, including activated Notch intracellular domain (NICD), Notch ligands (Jagged1 and DLL4) and the target gene Hes1. We found that Notch activation was universal in proliferating astrocytes and that the Notch ligand Jagged1 was uniquely upregulated in proliferating microglia, while DLL4 expression was increased in both activated astrocytes and degenerating oligodendrocytes. Our results indicate that microglia may play an important role in the intercellular receptor-ligand interaction of the Notch signaling pathway and contribute to the pathogenesis of motor neuron loss in ALS mice. Further experiments are required to clarify the exact mechanism responsible for Notch dysfunction in ALS.

中文翻译：

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在SOD1-G93A ALS模型小鼠的脊髓中，Notch信号通路的激活和Notch信号分子的细胞定位。

肌萎缩性侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征在于脊髓，脑干和皮质的运动神经元丢失和神经胶质增生。据报道，Notch信号通路在包括ALS在内的神经退行性疾病中是功能失调的。但是，确切的机制仍不清楚。在这里，我们检测到了增殖的神经胶质细胞中的Notch信号激活，SOD1-G93A模型脊髓中运动神经元的Notch失活以及Notch通路信号分子的细胞重新定位的剧烈变化，包括激活的Notch细胞内结构域（NICD），Notch配体（Jagged1和DLL4）和目标基因Hes1。我们发现，Notch激活在增殖星形胶质细胞中普遍存在，并且Notch配体Jagged1在增殖小胶质细胞中独特上调，而在活化的星形胶质细胞和退化的少突胶质细胞中DLL4的表达均增加。我们的结果表明，小胶质细胞可能在Notch信号通路的细胞间受体-配体相互作用中起重要作用，并有助于ALS小鼠运动神经元的丧失。需要进一步的实验来阐明导致ALS Notch功能障碍的确切机制。