Oral apolipoprotein A-I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer's disease.
Oral apolipoprotein A-I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer's disease.
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DOI：
10.1016/j.nbd.2009.03.007
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发表时间：
2009-06
影响因子：
6.1
通讯作者：
Anantharamaiah GM
中科院分区：
文献类型：
--
作者：
Handattu SP;Garber DW;Monroe CE;van Groen T;Kadish I;Nayyar G;Cao D;Palgunachari MN;Li L;Anantharamaiah GM
最近的证据表明，炎症可能在阿尔茨海默病（AD）的发病机制中起重要作用。由于载脂蛋白a - i模拟肽D-4F已被证明可以抑制动脉粥样硬化病变的形成和恢复已经存在的病变（在普伐他汀存在的情况下），并且该肽还可以减少脑小动脉炎症，我们进行了一项研究，以评估口服D-4F与普伐他汀共同给药对APPSwe-PS1ΔE9小鼠认知功能和海马中β淀粉样蛋白（a β）负担的疗效。三组雄性小鼠分别给予D-4F和普伐他汀、加炒D-4F （ScD-4F，一种对照肽）和普伐他汀的饮水，单独饮水作为对照组。Morris水迷宫实验中，D-4F+他汀类药物组动物的逃避潜伏期明显短于其他两组。对照组和sd - 4f +他汀组海马区Aβ负荷分别为4.2±0.5和3.8±0.6%，而sd - 4f +他汀组海马区Aβ负荷仅为1.6±0.1%。此外，口服D-4F+他汀类药物治疗后，激活的小胶质细胞数量（与其他两组相比p<0.05）和激活的星形胶质细胞数量（与对照组相比p<0.05）均显著减少。与其他两组相比，D-4F+他汀组炎症标志物TNFα和IL-1β水平显著降低（IL-1β与其他两组相比p<0.01， TNF-α与对照组相比p<0.001）， D-4F+他汀组MCP-1表达也低于其他两组。这些结果表明，载脂蛋白A-I模拟肽抑制淀粉样蛋白β沉积，并通过发挥大脑的抗炎特性改善认知功能。
Recent evidence indicates that inflammation may significantly contribute to the pathogenesis of Alzheimer’s disease (AD). Since the apo A-I mimetic peptide D-4F has been shown to inhibit atherosclerotic lesion formation and regress already existing lesions (in the presence of pravastatin) and the peptide also decreases brain arteriole inflammation, we undertook a study to evaluate the efficacy of oral D-4F co-administered with pravastatin on cognitive function and amyloid β (Aβ) burden in the hippocampus of APPSwe-PS1ΔE9 mice. Three groups of male mice were administered D-4F and pravastatin, Scrambled D-4F (ScD-4F, a control peptide) and pravastatin in drinking water, while drinking water alone served as control. The escape latency in the Morris Water Maze test was significantly shorter for the D-4F+statin administered animals compared to the other two groups. While the hippocampal region of the brain was covered with 4.2±0.5 and 3.8±0.6% of Aβ load in the control and ScD-4F+statin administered groups, in the D-4F+statin administered group Aβ load was only 1.6±0.1%. Furthermore, there was a significant decrease in the number of activated microglia (p<0.05 vs the other two groups) and activated astrocytes (p<0.05 vs control) upon oral D-4F+statin treatment. Inflammatory markers TNFα and IL-1β levels were decreased significantly in the D-4F+statin group compared to the other two groups (for IL-1β p<0.01 vs the other two groups and for TNF-α p<0.001 vs control) and the expression of MCP-1 were also less in D-4F+statin administered group compared to the other two groups. These results suggest that the apo A-I mimetic peptide inhibits amyloid β deposition and improves cognitive function via exerting anti-inflammatory properties in the brain.
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影响因子：
5.3
作者：
Hickman, Suzanne E.;Allison, Elizabeth K.;El Khoury, Joseph
通讯作者：
El Khoury, Joseph
影响因子：
158.5
作者：
in 't Veld, BA;Ruitenberg, A;Stricker, BHC
通讯作者：
Stricker, BHC
影响因子：
6
作者：
Coraci, IS;Husemann, J;El Khoury, JB
通讯作者：
El Khoury, JB
影响因子：
6.5
作者：
Buga, Georgette M.;Frank, Joy S.;Fogelman, Alan M.
通讯作者：
Fogelman, Alan M.
影响因子：
20.1
作者：
Gupta, H;Dai, LJ;White, CR
通讯作者：
White, CR