Astrocyte elevated gene-1 is a novel regulator of astrogliosis and excitatory amino acid transporter-2 via interplaying with nuclear factor-κB signaling in astrocytes from amyotrophic lateral sclerosis mouse model with hSOD1G93A mutation

Molecular and Cellular Neurosciences
Xiang YinHonglin Feng

Abstract

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 hSOD1G93A-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 ...Continue Reading

Citations

Feb 26, 2019·Neural Regeneration Research·Zhefan Stephen Chen, Ho Yin Edwin Chan
Sep 26, 2019·Neural Regeneration Research·Rachel KeryGregory W Kirschen

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