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在癌症研究方面受到了广泛关注。然而，人们对其在肌萎缩侧索硬化症（ALS）星形胶质细胞增生中的作用知之甚少。在本研究中，我们检测了 hSOD1 ^G93A阳性 (mut-SOD1) 星形胶质细胞和野生型 (wt-SOD1) 星形胶质细胞中 AEG-1 的表达，并打算阐明其在 ALS 相关星形胶质细胞增生和始终伴随的谷氨酸清除失调中的潜在功能。结果显示 mut-SOD1 星形胶质细胞中 AEG-1 的蛋白和 mRNA 水平升高；此外，mut-SOD1 星形胶质细胞中 NF-κB 信号通路相关蛋白和炎症细胞因子上调； AEG-1 敲低减弱星形胶质细胞增殖和促炎释放；我们还发现 AEG-1 沉默抑制了 p65 从细胞质到细胞核的易位，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）的表达水平显着降低，并伴有谷氨酸清除能力受损； yin yang 1 (YY1) 是 EAAT2 的转录抑制剂，在 mut-SOD1 星形胶质细胞的细胞核中增加。 AEG-1沉默抑制YY1向细胞核转位，增加EAAT2表达水平，增强星形胶质细胞清除谷氨酸的能力，最终发挥神经元保护作用。这项研究的结果暗示了 AEG-1 在 mut-SOD1 相关星形胶质细胞增生中的潜在功能以及 ALS 中伴随的兴奋性细胞毒性机制。