Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer's Disease Model Mice Targeting Beta-Amyloid Production.
Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer's Disease Model Mice Targeting Beta-Amyloid Production.
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Icariside II 针对 β-淀粉样蛋白的产生，有效减少阿尔茨海默病模型小鼠的空间学习和记忆障碍
DOI：
10.3389/fphar.2017.00106
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发表时间：
2017
影响因子：
5.6
通讯作者：
Gong Q
中科院分区：
文献类型：
--
作者：
Yan L;Deng Y;Gao J;Liu Y;Li F;Shi J;Gong Q
淫羊藿苷II（ICS II）是从淫羊藿中提取的一种具有广谱抗癌活性的天然化合物。近年来，ICS II在中枢神经系统的作用被研究，特别是在阿尔茨海默病（Alzheimer's disease，AD）中具有神经保护作用。在本研究中，我们试图研究ICS II对APPswe/PS1 dE 9（APP/PS1）双转基因小鼠的认知缺陷和β-淀粉样蛋白（Aβ）产生的影响。结果发现，慢性ICS II给药不仅有效地改善认知功能缺陷，而且还抑制神经元变性和减少斑块负荷的形成。ICS II通过上调去整合素和金属蛋白酶结构域10（ADAM 10）的表达，促进非淀粉样前体蛋白（APP）裂解过程，抑制Aβ生成;通过下调淀粉样前体蛋白（APP）和β位点淀粉样前体蛋白裂解酶1（BACE 1）的表达，抑制淀粉样APP加工途径。同时，ICS II减弱了过氧化物酶体增殖物激活受体γ（PPARγ）的降解以及对真核起始因子α磷酸化（p-eIF 2 α）和PKR内质网调节激酶磷酸化（p-PERK）的抑制。此外，磷酸二酯酶5型抑制剂（PDE 5-Is）最近已成为通过抑制Aβ水平来增强认知的可能治疗靶点，我们还发现ICS II显著降低磷酸二酯酶-5A（PDE 5A）表达。总之，本研究表明，ICS II可以减轻APP/PS1转基因小鼠的空间学习和记忆障碍。这种保护作用似乎是由于ADAM 10表达增加以及APP和BACE 1表达减少，导致海马和皮质中Aβ产生抑制。ICS II可抑制PPARγ降解和PERK/eIF 2 α磷酸化，有望成为治疗AD的有效药物。
Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer’s disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden. ICS II significantly suppressed Aβ production via promoting non-amyloidogenic APP cleavage process by up-regulating a disintegrin and metalloproteinase domain 10 (ADAM10) expression, inhibited amyloidogenic APP processing pathway by down-regulating amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1) expression in APP/PS1 transgenic mice. Meanwhile, ICS II attenuated peroxisome proliferator-activated receptor-γ (PPARγ) degradation as well as inhibition of eukaryotic initiation factor α phosphorylation (p-eIF2α) and PKR endoplasmic reticulum regulating kinase phosphorylation (p-PERK). Moreover, phosphodiesterase type 5 inhibitors (PDE5-Is) have recently emerged as a possible therapeutic target for cognitive enhancement via inhibiting Aβ levels, and we also found that ICS II markedly decreased phosphodiesterase-5A (PDE5A) expression. In conclusion, the present study demonstrates that ICS II could attenuate spatial learning and memory impairments in APP/PS1 transgenic mice. This protection appears to be due to the increased ADAM10 expression and decreased expression of both APP and BACE1, resulting in inhibition of Aβ production in the hippocampus and cortex. Inhibition of PPARγ degradation and PERK/eIF2α phosphorylation are involved in the course, therefore suggesting that ICS II might be a promising potential compound for the treatment of AD.
影响因子：
15.1
作者：
Sjölander A;Zetterberg H;Andreasson U;Minthon L;Blennow K
通讯作者：
Blennow K