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PGC-1α或有利于靶向Aβ的神经毒性 | BMC Neuroscience |
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论文标题：PPARγ coactivator-1α (PGC-1α) protects neuroblastoma cells against amyloid-beta (Aβ) induced cell death and neuroinflammation via NF-κB pathway
期刊：
作者：Yuqin Zhang, Changchun Chen, Yanliu Jiang, Shupei Wang, Xiaoyu Wu and Kai Wang
发表时间：2017/09/25
数字识别码：10.1186/s12868-017-0387-7
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阿尔茨海默病以β淀粉样蛋白（Aβ）沉积和神经元纤维缠结形成为特征。 Aβ是老年斑的重要组成成分，主要参与神经元死亡和神经炎症。过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）是重要的转录共激活因子之一，已证实其与能量代谢、心血管疾病和神经退行性疾病等密切相关。
在发表于BMC Neuroscience的一篇文章PPARγ coactivator-1α (PGC-1α) protects neuroblastoma cells against amyloid-beta (Aβ) induced cell death and neuroinflammation via NF-κB pathway中，来自安徽医科大学第一附属医院的Kai Wang及其同事发现，PGC-1α可能有利于靶向Aβ的神经毒性。
图一：Aβ1–42影响神经母细胞瘤N2a细胞中的PGC-1α表达。
Aβ1–42可在蛋白质和RNA水平减少神经母细胞瘤N2a细胞中的PGC-1α表达。Aβ1–42诱导裂解的caspase-3强烈活化，而PGC-1α则抑制其活化，保护N2a细胞免于Aβ诱导的细胞凋亡。PGC-1α过表达显著降低了一些重要促炎细胞因子的表达水平。此外，PGC-1α还抑制了NF-κB p65从细胞质到细胞核的转运以及Aβ1–42诱导的IκBα降解。
图二：PGC-1α对Aβ1–42诱导的神经母细胞瘤细胞死亡的影响。
这项研究结果表明，PGC-1α可以保护神经母细胞瘤细胞免于Aβ诱导的神经元凋亡和神经炎症。此外，PGC-1α的这种神经保护作用可通过NF-κB通路调节。综上所述，本研究的证据表明，PGC-1α可能有利于靶向Aβ的神经毒性。
摘要：
Background
Alzheimer’s disease is characterized by the accumulation of amyloid beta (Aβ) and the formation of neurofibrillary tangles. Aβ is the main constituent of senile plaques and is largely involved in neuronal death and neuroinflammation. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is one of the main transcriptional coactivator and has been related to many fields such as energy metabolism, cardiovascular disease, neurodegenerative disorders, and so on.
Results
Treatment with Aβ1–42 reduced the expression of PGC-1α in both protein and RNA levels of neuroblastoma N2a cells. Aβ1–42 induced a robust activation of cleaved caspase-3 while PGC-1α suppressed this activation and protected N2a cells from Aβ-induced cell death. Overexpression of PGC-1α significantly reduced the level of main proinflammatory cytokines. In addition, PGC-1α inhibited the transportation of NF-κB p65 from cytoplasm to nucleus and IκBα degradation induced by Aβ1–42.
Conclusion
Our results have demonstrated that PGC-1α can protect neuroblastoma cells against Aβ-induced neuronal death and neuroinflammation. Moreover, this neuroprotective effect of PGC-1α is regulated through NF-κB pathway. Taken together, our work provides evidence that PGC-1α could be beneficial in targeting Aβ neurotoxicity.
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期刊介绍:
BMC Neuroscience (, 2.173 - , 2.756 - ) is an open access, peer-reviewed journal that considers articles on all aspects of the nervous system, including molecular, cellular, developmental and animal model studies, as well as cognitive and behavioral research, and computational modeling.
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