PDF(Pubmed)
Abstract：
Risk factors such as dysregulation of Insulin-like growth factor (IGF) signaling have been linked to Alzheimer\'s disease. Here we show that Insulin-like Growth Factor Binding Protein 5 (Igfbp5), an inhibitory binding protein for insulin-like growth factor 1 (Igf-1) accumulates in hippocampal pyramidal neurons and in amyloid plaques in brains of Alzheimer patients. We investigated the pathogenic relevance of this finding with transgenic mice overexpressing Igfbp5 in pyramidal neurons of the brain. Neuronal overexpression of Igfbp5 prevents the training-induced increase of hippocampal and cortical Bdnf expression and reduces the effects of exercise on memory retention, but not on learning acquisition. Hence, elevated IGFBP5 expression could be responsible for some of the early cognitive deficits that occur during the course of Alzheimer\'s disease.
摘要：
诸如胰岛素样生长因子（IGF）信号调节异常等危险因素与阿尔茨海默病有关。在这里，我们显示胰岛素样生长因子结合蛋白5（Igfbp5），胰岛素样生长因子1（Igf-1）的抑制性结合蛋白在阿尔茨海默病患者的海马锥体神经元和淀粉样斑块中积累。我们研究了这一发现与在大脑锥体神经元中过表达Igfbp5的转基因小鼠的致病性相关性。神经元过表达Igfbp5可防止训练引起的海马和皮质Bdnf表达增加，并降低运动对记忆保留的影响，但不是学习习得。因此，升高的IGFBP5表达可能是阿尔茨海默病过程中发生的一些早期认知缺陷的原因。
