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首页> 外文期刊>Neurobiology of disease >Silencing of ICERs (Inducible cAMP Early Repressors) results in partial protection of neurons from programmed cell death
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Silencing of ICERs (Inducible cAMP Early Repressors) results in partial protection of neurons from programmed cell death

机译：沉默ICERs（诱导型cAMP早期阻遏物）可部分保护神经元免受程序性细胞死亡

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摘要

ICERs proteins (Inducible cAMP Early Repressors) are the most effective endogenous repressors of CREB/CREM/ATF transcription factors family (CREB-cAMP Responsive Element Binding protein, CREM-cAMP Responsive Element Modulator, ATF-Activating Transcription Factor) that have repeatedly been shown to have a prosurvival function. It has been reported previously that neuronal death is accompanied by increased expression of ICERs and, furthermore, their overexpression provokes neuronal cell death in culture. However, it was not explained whether endogenously activated by proapoptotic stimuli ICERs contribute to the neuronal cell death. Herein, we have examined the involvement of endogenous ICERs in the apoptosis by checking whether it is possible to protect neurons from cell death by blocking the ICER gene.We applied two different in vitro models of neuronal death of primary neuronal cultures: excitotoxic death of neurons derived from dentate gyrus, and cortical cell loss provoked by trophic deprivation. Using the lentiviral vector (LV) to deliver shRNA, specifically silencing ICERs, but not other CREM proteins, we have found that silencing of ICERs enhances the CRE-driven transcription and exerts a mild, although significant, neuroprotective effect in both models. Since we demonstrated that silencing of endogenous ICERs have protective effect on neurons exposed to apoptosis-provoking conditions, targeting ICERs might be a novel strategy to prevent neuronal loss during degenerative processes.
机译：ICERs蛋白（诱导型cAMP早期阻遏物）是CREB ​​/ CREM / ATF转录因子家族（CREB-cAMP响应元件结合蛋白，CREM-cAMP响应元件调节剂，ATF激活转录因子）最有效的内源性阻遏物。具有生存功能。先前已有报道，神经元死亡伴随着ICERs表达的增加，此外，它们的过表达在培养中引起神经元细胞死亡。然而，没有解释由凋亡促发性ICERs内源性激活是否导致神经元细胞死亡。在本文中，我们通过检查是否有可能通过阻断ICER基因来保护神经元免受细胞死亡来检查内源性ICER与细胞凋亡的关系。我们应用了两种不同的体外原代神经元培养物神经元死亡模型：神经元的兴奋性中毒死亡源自齿状回和营养缺乏引起的皮质细胞丢失。使用慢病毒载体（LV）递送shRNA，特别是沉默ICERs，但不沉默其他CREM蛋白，我们发现，沉默ICERs可以增强CRE驱动的转录，并且在两种模型中均具有轻度但重要的神经保护作用。由于我们证明了沉默内源性ICERs对暴露于引起细胞凋亡的神经元具有保护作用，因此靶向ICERs可能是防止变性过程中神经元丢失的一种新策略。

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