School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Institute of Life Science & Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea.
Department of Neural Development and Disease, Department of Structure & Function of Neural Network, Korea Brain Research Institute, Daegu, 41062, Republic of Korea.
Cell Death Dis. 2018 May 1;9(5):449. doi: 10.1038/s41419-018-0491-3.
The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson's disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons. Moreover, the neuroprotection conferred by the AEG-1 upregulation significantly intensified the neurorestorative effects of the constitutively active ras homolog enriched in the brain [Rheb(S16H)]. Collectively, these results demonstrated that the sustained level of AEG-1 as an important anti-apoptotic factor in nigral DA neurons might potentiate the therapeutic effects of treatments, such as Rheb(S16H) administration, on the degeneration of the DA pathway that characterizes PD.
星形胶质细胞上调基因-1（AEG-1）在黑质多巴胺（DA）神经元中的作用尚未研究。在这里，我们报告称，与年龄匹配的对照组相比，帕金森病（PD）患者死后黑质中的 DA 神经元中 AEG-1 的表达明显降低。在 6-羟多巴胺（6-OHDA）诱导的 PD 小鼠模型中也发现了 AEG-1 水平降低。腺相关病毒诱导的 AEG-1 表达增加可减轻 6-OHDA 触发的黑质 DA 神经元凋亡性死亡。此外，AEG-1 上调赋予的神经保护作用显著增强了脑丰富的组成性激活 Ras 同源物（Rheb[S16H]）的神经修复作用。总之，这些结果表明，AEG-1 的持续水平作为黑质 DA 神经元中的重要抗凋亡因子，可能增强 Rheb[S16H]给药等治疗方法对 PD 特征性 DA 通路变性的治疗效果。
