Activation of α7 nAChR by PNU-282987 improves synaptic and cognitive functions through restoring the expression of synaptic-associated proteins and the CaM-CaMKII-CREB signaling pathway
Activation of α7 nAChR by PNU-282987 improves synaptic and cognitive functions through restoring the expression of synaptic-associated proteins and the CaM-CaMKII-CREB signaling pathway
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PNU-282987 激活 α7 nAChR 通过恢复突触相关蛋白和 CaM-CaMKII-CREB 信号通路的表达来改善突触和认知功能
DOI：
10.18632/aging.102640
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Qi XL
中科院分区：
文献类型：
--
作者：
Wang XL;Deng YX;Gao YM;Dong YT;Wang F;Guan ZZ;Hong W;Qi XL
Ligands of nicotinic acetylcholine receptors (nAChRs) are widely considered as potential therapeutic agents. The present study used primary hippocampus cells and APPswe/PSEN1dE9 double-transgenic mice models to study the possible therapeutic effect and underlying mechanism of the specific activation of α7 nAChR by PNU-282987 in the pathogenesis of Alzheimer’s disease. The results indicated that activation of α7 nAChR attenuated the Aβ-induced cell apoptosis, decreased the deposition of Aβ, increased the expression of synaptic-associated proteins, and maintained synaptic morphology. Furthermore, in the APP/PS1_DT mice model, activation of α7 nAChR attenuated Aβ-induced synaptic loss, reduced the deposition of Aβ in the hippocampus, maintained the integral structure of hippocampus-derived synapse, and activated the calmodulin (CaM)-calmodulin-dependent protein kinase II (CaMKII)-cAMP response element-binding protein signaling pathway by upregulation of its key signaling proteins. In addition, activation of α7 nAChR improved the learning and memory abilities of the APP/PS1_DT mice. Collectively, the activation of α7 nAChR by PNU-282987 attenuated the toxic effect of Aβ in vivo and in vitro, which including reduced deposition of Aβ in the hippocampus, maintained synaptic morphology by partially reversing the expression levels of synaptic-associated proteins, activation of the Ca2+ signaling pathway, and improvement of the cognitive abilities of APP/PS1_DT mice.
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影响因子：
5.8
作者：
Overk, Cassia R.;Masliah, Eliezer
通讯作者：
Masliah, Eliezer
影响因子：
5.2
作者：
Sawda C;Moussa C;Turner RS
通讯作者：
Turner RS
影响因子：
4.6
作者：
Yuki D;Sugiura Y;Zaima N;Akatsu H;Takei S;Yao I;Maesako M;Kinoshita A;Yamamoto T;Kon R;Sugiyama K;Setou M
通讯作者：
Setou M
影响因子：
3.4
作者：
S. McGurk;E. Levin;L. Butcher
通讯作者：
S. McGurk;E. Levin;L. Butcher
影响因子：
4
作者：
Pchitskaya E;Popugaeva E;Bezprozvanny I
通讯作者：
Bezprozvanny I