CART modulates beta-amyloid metabolism-associated enzymes and attenuates memory deficits in APP/PS1 mice
CART modulates beta-amyloid metabolism-associated enzymes and attenuates memory deficits in APP/PS1 mice
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CART 调节 β-淀粉样蛋白代谢相关酶并减轻 APP/PS1 小鼠的记忆缺陷
DOI：
10.1080/01616412.2017.1348689
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发表时间：
2017-07
影响因子：
1.9
通讯作者：
Xu Yun
中科院分区：
文献类型：
--
作者：
Yin Kailin;Jin Jiali;Zhu Xiaolei;Yu Linjie;Wang Sulei;Qian Lai;Han Lijuan;Xu Yun
摘要简介：可卡因和安非他明调节转录（CART）肽已被证明对中风和一些神经退行性疾病发挥神经保护作用。在当前的研究中，我们研究了 CART 对 APP/PS1 小鼠的保护作用和潜在机制。方法：采用酶联免疫吸附法测定APP/PS1小鼠海马CART、可溶性Aβ1-40和Aβ1-42蛋白水平。我们使用实时 PCR 和蛋白质印迹法测定了 APP/PS1 小鼠海马中 Aβ 代谢相关酶的 mRNA 和蛋白水平，包括脑啡肽酶 (NEP)、胰岛素降解酶 (IDE)、晚期糖基化终末产物受体 (RAGE) 和低密度脂蛋白受体相关蛋白 1 (LRP-1)。使用 Morris 水迷宫测量 APP/PS1 小鼠的空间记忆。使用蛋白质印迹法测定 AKT、ERK、p38 和 JNK 的磷酸化。结果：CART治疗后APP/PS1小鼠海马可溶性Aβ1-40和Aβ1-42水平显着降低。 CART 调节 NEP、IDE、RAGE 和 LRP-1 的水平。此外，CART抑制MAPK通路并激活AKT通路，而抑制AKT通路则降低IDE和LRP-1的水平。此外，CART 减轻了 APP/PS1 小鼠的空间记忆缺陷。结论:CART通过调节Aβ代谢相关酶的表达降低APP/PS1小鼠海马可溶性Aβ水平,其机制可能与MAPK和AKT通路有关。
Abstract Introduction: Cocaine- and amphetamine-regulated transcript (CART) peptide has been demonstrated to exert neuroprotective effects in stroke and some neurodegeneration diseases. In current study, we investigated the protective effects and underlying mechanisms of CART in APP/PS1 mice. Methods: The protein levels of CART, soluble Aβ1–40 and Aβ1–42 were measured in the hippocampus of APP/PS1 mice by enzyme-linked immunosorbent assay. We determined the mRNA and protein levels of Aβ metabolism-associated enzymes including neprilysin (NEP), insulin-degrading enzyme (IDE), receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP-1) in the hippocampus of APP/PS1 mice using real-time PCR and western blotting. Spatial memory was measured in APP/PS1 mice using the Morris water maze. The phosphorylation of AKT, ERK, p38, and JNK was determined using western blotting. Results: The levels of soluble Aβ1–40 and Aβ1–42 were significantly decreased in the hippocampus of APP/PS1 mice after CART treatment. CART modulated the levels of NEP, IDE, RAGE, and LRP-1. In addition, CART inhibited the MAPK pathways and activated the AKT pathway, whereas inhibition of the AKT pathway decreased the levels of IDE and LRP-1. Furthermore, CART attenuated spatial memory deficits in the APP/PS1 mice. Conclusion: CART decreases the levels of soluble Aβ in the hippocampus of APP/PS1 mice by modulating the expression of Aβ metabolism-associated enzymes, which may be associated with the MAPK and AKT pathways.
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影响因子：
64.8
作者：
Roy DS;Arons A;Mitchell TI;Pignatelli M;Ryan TJ;Tonegawa S
通讯作者：
Tonegawa S
感觉网络功能障碍，行为障碍及其在阿尔茨海默氏症的β-淀粉样变性小鼠模型中的可逆性。
DOI：
10.1523/jneurosci.2085-11.2011
发表时间：
2011-11-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Wesson DW;Borkowski AH;Landreth GE;Nixon RA;Levy E;Wilson DA
通讯作者：
Wilson DA
影响因子：
2.3
作者：
Moffett, Mark C.;Song, Jane;Kuhar, Michael J.
通讯作者：
Kuhar, Michael J.
影响因子：
2.4
作者：
Maletínská L;Maixnerová J;Matysková R;Haugvicová R;Pirník Z;Kiss A;Zelezná B
通讯作者：
Zelezná B
影响因子：
5.3
作者：
Wang, J;Dickson, DW;Lee, VMY
通讯作者：
Lee, VMY