1. Gx-50 Inhibits Neuroinflammation via α7 nAChR Activation of the JAK2/STAT3 and PI3K/AKT Pathways.
- Author
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Shi Shi, Dongli Liang, Min Bao, Yilin Xie, Wangjie Xu, Lianyun Wang, Zhaoxia Wang, Zhongdong Qiao, Shi, Shi, Liang, Dongli, Bao, Min, Xie, Yilin, Xu, Wangjie, Wang, Lianyun, Wang, Zhaoxia, and Qiao, Zhongdong
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ALZHEIMER'S disease research , *BRAIN disease research , *NICOTINIC acetylcholine receptors , *INFLAMMATION , *NEURODEGENERATION , *PROTEIN metabolism , *RNA metabolism , *CHOLINERGIC receptors , *ACRYLAMIDE , *ANALYSIS of variance , *ANTI-inflammatory agents , *CELLS , *CELLULAR signal transduction , *CYTOKINES , *ENZYME inhibitors , *ENZYME-linked immunosorbent assay , *GENES , *PEPTIDES , *PHOSPHOTRANSFERASES , *PROTEINS , *PHARMACODYNAMICS - Abstract
Recent studies have revealed that the α7 nicotinic acetylcholine receptor (α7 nAChR) is a critical link between inflammation and neurodegeneration, which is closely associated with Alzheimer's disease (AD). The JAK2/STAT3 and PI3K/AKT signaling pathways contribute to the neuroprotective and anti-inflammatory effects of α7nAChR. Our previous studies have shown that treatment with gx-50 improves cognitive function and is neuroprotective. Here, we investigated the effect of gx-50 on α7 nAChR and Aβ-induced inflammation in microglia. First, the binding affinity of gx-50 to α7 nAChR was examined using the fluorescence-based Octet RED system, and the expression of α7 nAChR was detected using real-time PCR and western blotting. We also investigated downstream events of α7 nAChR activity, including the translocation of p-STAT3 and the phosphorylation of JAK2, STAT3, PI3K, and AKT. Finally, the effect of gx-50 on Aβ-induced inflammation via α7 nAChR-mediated signaling pathways was investigated using cytokine assays. The results showed that gx-50 is able to act as a specific ligand to activate α7 nAChR, which then upregulates the JAK2/STAT3 and PI3K/AKT signaling pathways to inhibit the secretions of pro-inflammatory cytokines, such as IL-1β. In conclusion, the results suggest that gx-50 could inhibit the Aβ-induced inflammatory response in microglia via α7 nAChR activity, which might be a successful therapeutic target against AD. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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