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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Distinct Roles of sAPP-α and sAPP-β in Regulating U251 Cell Differentiation

Author(s): Junfeng Jiang, Yue Wang, Lei Hou, Lixing Fan, Qiaoling Wang, Zhenyu Xu, Qing Sun and Houqi Liu

Volume 10 , Issue 7 , 2013

Page: [706 - 713] Pages: 8

DOI: 10.2174/15672050113109990141

Price: $65

Abstract

Sequential cleavages of APP by β-secretase and γ-secretase release β-amyloid (Aβ) and one secreted form of APP (sAPP-β) in Alzheimer’ s disease (AD). Alternatively, in non-pathological situations, APP is predominantly cleaved by α-secretase within the amyloid sequence, to release the other soluble form of APP, sAPP-α. However, the functions of the two types of sAPP are still unclear. We performed this study to compare the function of sAPP-α and sAPP-β in differentiation of the glioma cell line U251. We found that sAPP-α suppressed astrocytic differentiation and promoted neuronal differentiation in U251 cells. Additionally, sAPP-α enhanced U251 terminal differentiation into a cholinergic-like neuronal phenotype. In contrast, sAPP-β suppressed neuronal differentiation and promoted the astrocytic differentiation of U251 cells. These findings could not only enrich the knowledge of the potential physiological function of sAPP-α and sAPP-β, but also indicate that they may be connected to the pathological mechanism of AD. Furthermore, these findings suggest that new strategies, such as increasing the level of sAPP-α and/or decreasing the level of sAPP-β in brain, or transplanting stem cells with increased sAPP-α and/or decreased sAPP-β, may have potential value for AD treatment.

Keywords: Alzheimer’ s disease, APP, sAPP-α, sAPP-β, neural stem cells, U251, glioma, differentiation, down syndrome.


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