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.
Current Alzheimer Research
Title:Distinct Roles of sAPP-α and sAPP-β in Regulating U251 Cell Differentiation
Volume: 10 Issue: 7
Author(s): Junfeng Jiang, Yue Wang, Lei Hou, Lixing Fan, Qiaoling Wang, Zhenyu Xu, Qing Sun and Houqi Liu
Affiliation:
Keywords: Alzheimer’ s disease, APP, sAPP-α, sAPP-β, neural stem cells, U251, glioma, differentiation, down syndrome.
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.
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Jiang Junfeng, Wang Yue, Hou Lei, Fan Lixing, Wang Qiaoling, Xu Zhenyu, Sun Qing and Liu Houqi, Distinct Roles of sAPP-α and sAPP-β in Regulating U251 Cell Differentiation, Current Alzheimer Research 2013; 10 (7) . https://dx.doi.org/10.2174/15672050113109990141
DOI https://dx.doi.org/10.2174/15672050113109990141 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
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Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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