Regulation of global gene expression and cell proliferation by APP.

Scientific reports (2016-03-05)
Yili Wu, Si Zhang, Qin Xu, Haiyan Zou, Weihui Zhou, Fang Cai, Tingyu Li, Weihong Song
ABSTRACT

Down syndrome (DS), caused by trisomy of chromosome 21, is one of the most common genetic disorders. Patients with DS display growth retardation and inevitably develop characteristic Alzheimer's disease (AD) neuropathology, including neurofibrillary tangles and neuritic plaques. The expression of amyloid precursor protein (APP) is increased in both DS and AD patients. To reveal the function of APP and elucidate the pathogenic role of increased APP expression in DS and AD, we performed gene expression profiling using microarray method in human cells overexpressing APP. A set of genes are significantly altered, which are involved in cell cycle, cell proliferation and p53 signaling. We found that overexpression of APP inhibits cell proliferation. Furthermore, we confirmed that the downregulation of two validated genes, PSMA5 and PSMB7, inhibits cell proliferation, suggesting that the downregulation of PSMA5 and PSMB7 is involved in APP-induced cell proliferation impairment. Taken together, this study suggests that APP regulates global gene expression and increased APP expression inhibits cell proliferation. Our study provides a novel insight that APP overexpression may contribute to the growth impairment in DS patients and promote AD pathogenesis by inhibiting cell proliferation including neural stem cell proliferation and neurogenesis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Amyloid Precursor Protein, C-Terminal antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Acetyl-Amyloid β 25-35
Sigma-Aldrich
Monoclonal Anti-APP antibody produced in mouse, clone 2C12, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-β-Amyloid Protein (1-40) antibody produced in rabbit, whole antiserum