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.
Aging (Albany NY)
; 12(1): 543-570, 2020 01 06.
Article
em En
| MEDLINE
| ID: mdl-31905173
ABSTRACT
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 Aß-induced cell apoptosis, decreased the deposition of Aß, increased the expression of synaptic-associated proteins, and maintained synaptic morphology. Furthermore, in the APP/PS1_DT mice model, activation of α7 nAChR attenuated Aß-induced synaptic loss, reduced the deposition of Aß 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 Aß in vivo and in vitro, which including reduced deposition of Aß 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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MEDLINE
Assunto principal:
Benzamidas
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Compostos Bicíclicos com Pontes
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Transdução de Sinais
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Cognição
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Transmissão Sináptica
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Agonistas Nicotínicos
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina
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Receptor Nicotínico de Acetilcolina alfa7
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article