神经炎症
转基因小鼠
神经保护
药理学
转基因
体内
淀粉样前体蛋白
发病机制
化学
医学
神经科学
阿尔茨海默病
内分泌学
内科学
炎症
生物
疾病
生物化学
生物技术
基因
作者
Jing Liu,Ye Lin,Yang Yang,Yane Guo,Yi Shang,Bo Zhou,Tianlong Liu,Junfen Fan,Chao Wei
标识
DOI:10.1016/j.bcp.2022.115149
摘要
Growing evidence indicates that inflammatory damage is implicated in the pathogenesis of Alzheimer's disease (AD). Z-Guggulsterone (Z-GS) is a natural steroid, which is extracted from Commiphora mukul and has anti-inflammatory effects in vivo and in vitro. In the present study, we investigated the disease-modifying effects of chronic Z-GS administration on the cognitive and neuropathological impairments in the transgenic mouse models of AD. We found that chronic Z-GS administration prevented learning and memory deficits in the APPswe/PS1dE9 mice. In addition, Z-GS treatment significantly decreased cerebral amyloid-β (Aβ) levels and plaque burden via inhibiting amyloid precursor protein (APP) processing by reducing beta-site APP cleaving enzyme 1 (BACE1) expression in the APPswe/PS1dE9 mice. We also found that Z-GS treatment markedly alleviated neuroinflammation and reduced synaptic defects in the APPswe/PS1dE9 mice. Furthermore, the activated TLR4/NF-κB signaling pathways in APPswe/PS1dE9 mice were remarkably inhibited by Z-GS treatment, which was achieved via suppressing the phosphorylation of JNK. Collectively, our data demonstrate that chronic Z-GS treatment restores cognitive defects and reverses multiple neuropathological impairments in the APPswe/PS1dE9 mice. This study provides novel insights into the neuroprotective effects and neurobiological mechanisms of Z-GS on AD, indicating that Z-GS is a promising disease-modifying agent for the treatment of AD.
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