PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is characterized by the deposition in the brain of senile plaques composed of amyloid-β peptides (Aβs) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE), has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 for 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1, and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme, was also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.
摘要：
阿尔茨海默病（AD）的特征是由淀粉样β肽（Aβs）组成的老年斑在大脑中沉积，从而增加炎症。一种源自胰岛素样生长因子（IGF）-I的内源性肽，甘氨酸-脯氨酸-谷氨酸（GPE），具有IGF-I致敏和神经保护作用。这里,我们研究了GPE对卵巢切除大鼠脑室内输注Aβ25-352周(300pmol/d)产生的Aβ水平和海马炎症的影响,以及与这些GPE相关作用相关的信号通路和Aβ降解酶水平.GPE阻止了Aβ诱导的p38丝裂原活化蛋白激酶磷酸化的增加以及信号转导和转录激活因子3，胰岛素受体底物1和Akt的激活的减少，以及海马中白介素（IL）-2和IL-13的水平。生长抑素的功能，以抑制腺苷酸环化酶活性的百分比和胰岛素降解酶的水平来衡量，也通过GPE共同处理保存。这些发现表明，GPE共同给药可以通过调节瘦素和IGF-I信号传导途径来改变海马细胞因子含量和生长抑素功能，从而防止Aβ损伤，这些途径可以通过调节Aβ蛋白酶的水平和/或活性来影响Aβ水平的降低。
