AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1^G93A-positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling. Besides, excitatory amino acid transporter-2 (EAAT2) expression levels were significantly decreased, accompanied by impaired glutamate clearance ability, in mut-SOD1 astrocytes; yin yang 1 (YY1), a transcriptional inhibitor for EAAT2, increased in nucleus of mut-SOD1 astrocytes. AEG-1 silence inhibited translocation of YY1 to nucleus, increased EAAT2 expression levels, and enhanced astrocytic ability of glutamate clearance, ultimately exerted the neuronal protection. Findings from this study implicate potential function of AEG-1 in mut-SOD1 related astrogliosis and the accompanied excitatory cytotoxic mechanism in ALS.

AEG-1在癌症研究中受到广泛关注。然而，对其在肌萎缩性侧索硬化症（ALS）星形胶质增生中的作用了解甚少。在这项研究中，我们检测到hSOD1 ^G93A中的AEG-1表达-阳性（mut-SOD1）星形胶质细胞和野生型（wt-SOD1）星形胶质细胞，并打算阐明其在ALS相关的星形胶质细胞增生和总是伴有谷氨酸清除失调的潜在功能。结果显示mut-SOD1星形胶质细胞中AEG-1的蛋白质和mRNA水平升高。另外，mut-SOD1星形胶质细胞中NF-κB信号通路相关蛋白和炎性细胞因子被上调。AEG-1基因敲低减弱了星形胶质细胞的增殖和促炎性释放；我们还发现AEG-1沉默抑制p65从细胞质向核的移位，这与抑制NF-κB信号传导有关。此外，mut-SOD1星形胶质细胞中兴奋性氨基酸转运蛋白2（EAAT2）的表达水平明显降低，同时谷氨酸清除能力受损。阴阳1（YY1），EAAT2的转录抑制剂在mut-SOD1星形胶质细胞的核中增加。AEG-1沉默抑制YY1向核的移位，增加EAAT2表达水平，并增强谷氨酸清除的星形细胞能力，最终发挥了神经元保护作用。这项研究的发现暗示了AEG-1在mut-SOD1相关的星形胶质细胞增生中的潜在功能，以及在ALS中伴随的兴奋性细胞毒性机制。