Distinct Roles of sAPP-alpha and sAPP-beta in Regulating U251 Cell Differentiation

作者：Jiang Junfeng; Wang Yue; Hou Lei; Fan Lixing; Wang Qiaoling; Xu Zhenyu; Sun Qing; Liu Houqi^*

来源：Current Alzheimer Research, 2013, 10(7): 706-713.

• Alzheimer's disease
• APP
• sAPP-alpha
• sAPP-beta
• neural stem cells
• U251
• glioma
• differentiation
• down syndrome

Sequential cleavages of APP by beta-secretase and gamma-secretase release beta-amyloid (A beta) and one secreted form of APP (sAPP-beta) in Alzheimer's disease (AD). Alternatively, in non-pathological situations, APP is predominantly cleaved by alpha-secretase within the amyloid sequence, to release the other soluble form of APP, sAPP-alpha. However, the functions of the two types of sAPP are still unclear. We performed this study to compare the function of sAPP-alpha and sAPP-beta in differentiation of the glioma cell line U251. We found that sAPP-alpha suppressed astrocytic differentiation and promoted neuronal differentiation in U251 cells. Additionally, sAPP-alpha enhanced U251 terminal differentiation into a cholinergic-like neuronal phenotype. In contrast, sAPP-beta 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-alpha and sAPP-beta, 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-alpha and/or decreasing the level of sAPP-beta in brain, or transplanting stem cells with increased sAPP-alpha and/or decreased sAPP-beta, may have potential value for AD treatment.

• 出版日期2013-9
• 单位中国人民解放军第二军医大学