P7C3 Inhibits LPS-Induced Microglial Activation to Protect Dopaminergic Neurons Against Inflammatory Factor-Induced Cell Death in vitro and in vivo.
P7C3 Inhibits LPS-Induced Microglial Activation to Protect Dopaminergic Neurons Against Inflammatory Factor-Induced Cell Death in vitro and in vivo.
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P7C3 抑制 LPS 诱导的小胶质细胞激活，以保护多巴胺能神经元在体外和体内免受炎症因子诱导的细胞死亡。
DOI：
10.3389/fncel.2018.00400
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发表时间：
2018
影响因子：
5.3
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Gu C;Hu Q;Wu J;Mu C;Ren H;Liu CF;Wang G
帕金森病 (PD) 是第二常见的神经退行性疾病。尽管其发病机制尚不清楚，但越来越多的证据表明小胶质细胞介导的神经炎症对帕金森病的进展有很大影响。 P7C3 是一种氨基丙基咔唑，在包括 PD 在内的多种神经退行性疾病动物模型中具有显着的神经保护作用。在这项研究中，我们旨在研究 P7C3 对神经炎症的影响。我们发现，P7C3 特别抑制脂多糖（LPS）诱导的促炎因子的表达，但不影响小胶质细胞中的抗炎因子。 P7C3 的抗炎作用机制涉及核因子 κB (NF-κB) 信号通路的抑制。小胶质细胞中 P7C3 的预处理可以减弱 LPS 诱导的 IκB 激酶 (IKK) 激活、抑制性 κB α (IκBα) 降解和 NF-κB 核转位。此外，在 LPS 处理的小胶质细胞中，P7C3 预处理降低了条件培养基对 MES23.5 细胞（多巴胺能 (DA) 细胞系）的毒性。最重要的是，在 LPS 刺激的小鼠模型中观察到 P7C3 的抗炎作用。总的来说，我们的研究表明P7C3在体内和体外通过抑制NF-κB通路来抑制LPS诱导的小胶质细胞活化，为P7C3的抗炎作用提供了理论基础。
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Although its pathogenesis remains unclear, growing evidencce suggests that microglia-mediated neuroinflammation contributes greatly to the progression of PD. P7C3, an aminopropyl carbazole, possesses significant neuroprotective effects in several neurodegenerative disease animal models, including PD. In this study, we designed to investigate the effects of P7C3 on neuroinflammation. We showed that P7C3 specially suppressed the expression of lipopolysaccharide (LPS)-induced pro-inflammatory factors but not influenced the anti-inflammatory factors in microglia. The inhibition of the nuclear factor κB (NF-κB) signaling pathway was involved in the mechanisms of the anti-inflammatory effects by P7C3. LPS-induced activation of IκB kinase (IKK), degradation of the inhibitory κB alpha (IκBα) and nuclear translocation of NF-κB can be attenuated by the pretreatment of P7C3 in microglia. Furthermore, in LPS-treated microglia, P7C3-pretreatment decreased the toxicity of conditioned media to MES23.5 cells (a dopaminergic (DA) cell line). Most importantly, the anti-inflammatory effects of P7C3 were observed in LPS-stimulated mouse model. In general, our study demonstrates that P7C3 inhibits LPS-induced microglial activation through repressing the NF-κB pathway both in vivo and in vitro, providing a theoretical basis for P7C3 in anti-inflammation.
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影响因子：
4
作者：
Hess, J;Angel, P;Schorpp-Kistner, M
通讯作者：
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影响因子：
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影响因子：
3.7
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Gao FS;Feng L;Zhang Q;Yan RQ;Li YG;Li XS
通讯作者：
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