Fwo memory associated genes regulated by amyloid precursor protein intracellular domain—Novel insights into the pathogenesis of learning and memory impairment in Alzheimer＇s disease

• Published in: 中国神经再生研究：英文版 2012, Vol.7 (5), p.341-346
• Main Author: Chuandong Zheng Xi Gu Zhimei Zhong Rui Zhu Tianming Gao Fang Wang
• Format: Article
• Language: English
• Subjects: 发病机理; 基因调控; 学习; 染色质免疫沉淀; 淀粉样前体蛋白; 结构域; 记忆障碍; 阿尔茨海默氏病
• ISSN: 1673-5374

In this study, we employed chromatin immunoprecipitation, a useful method for studying the locations of transcription factors bound to specific DNA regions in specific cells, to investigate amyloid precursor protein intracellular domain binding sites in chromatin DNA from hippocampal neurons of rats, and to screen out five putative genes associated with the learning and memory functions. The promoter regions of the calcium/calmodulin-dependent protein kinase II alpha and glutamate receptor-2 genes were amplified by PCR from DNA products immunoprecipitated by amyloid precursor protein intracellular domain. An electrophoretic mobility shift assay and western blot analysis suggested that the promoter regions of these two genes associated with learning and memory were bound by amyloid precursor protein intracellular domain （in complex form）. Our experimental findings indicate that the amyloid precursor protein intracellular domain is involved in the transcriptional regulation of learning- and memory-associated genes in hippocampal neurons. These data may provide new insights into the molecular mechanism underlying the symptoms of progressive memory loss in Alzheimer＇s disease.