Downregulated AEG-1 together with inhibited PI3K/Akt pathway is associated with reduced viability of motor neurons in an ALS model

文献类型： 外文期刊

第一作者： Yin, Xiang

作者： Yin, Xiang;Jiang, Haizhi;Wang, Shuyu;Jiang, Hongquan;Qi, Yan;Wang, Jing;Wang, Xudong;Dong, Guangtao;Feng, Honglin;Ren, Ming;Cui, Shangjin;Leeds, Peter;Chuang, De-Maw

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关键词： Amyotrophic lateral sclerosis (ALS);Astrocyte elevated gene-1 (AEG-1);CREB;PI3K/Akt pathway

期刊名称：MOLECULAR AND CELLULAR NEUROSCIENCE （ 影响因子：4.314； 五年影响因子：4.107 ）

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收录情况： SCI

摘要： Astrocyte elevated gene-1 (AEG-1) has been reported to regulate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and is also regulated by it. This study investigated how AEG-1 participates in the survival pathway of motor neurons in amyotrophic lateral sclerosis (ALS). We found reduced levels of AEG-1 in ALS motor neurons, both in vivo and in vitro, compared to wild type controls. Moreover, AEG-1 silencing demonstrated inhibition of the PI3K/Akt pathway and increased cell apoptosis. Additionally, the PI3K/Akt pathway in mSOD1 cells was unresponsive under serum deprivation conditions compared to wtSOD1 cells. These results suggest that AEG-1 deficiency, together with the inhibited PI3K/Akt pathway was associated with decreased viability of ALS motor neurons. However, the mRNA levels of AEG-1 were still lower in mSOD1 cells compared to the control groups, though the signaling pathway was activated by application of a PI3-K activator. This suggests that in ALS motor neurons, some unknown interruption exists in the PI3K/Akt/CREB/AEG-1 feedback loop, thus attenuating the protection by this signaling pathway. Together, these findings support that AEG-1 is a critical factor for cell survival, and the disrupted PI3K/Akt/CREB/AEG-1 cycle is involved in the death of injured motor neurons and pathogenesis of ALS. (C) 2015 Elsevier Inc. All rights reserved.

分类号： Q42`R741

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