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Role of cystatin C in amyloid precursor protein-induced proliferation of neural stem/progenitor cells

Citation

Hu, Y and Hung, AC and Cui, H and Dawkins, E and Bolos, M and Foa, L and Young, KM and Small, DH, Role of cystatin C in amyloid precursor protein-induced proliferation of neural stem/progenitor cells, Journal of Biological Chemistry, 288, (26) pp. 18853-18862. ISSN 0021-9258 (2013) [Refereed Article]


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Copyright Statement

Copyright 2013 The American Society for Biochemistry and Molecular Biology, Inc.

DOI: doi:10.1074/jbc.M112.443671

Abstract

The amyloid precursor protein (APP) is well studied for its role in Alzheimer's disease. However, little is known about its normal function. In this study, we examined the role of APP in neural stem/progenitor cell (NSPC) proliferation. NSPCs derived from APP-overexpressing Tg2576 transgenic mice proliferated more rapidly than NSPCs from the corresponding background strain (C57Bl/6xSJL) wild-type mice. In contrast, NSPCs from APP knockout (APP-KO) mice had reduced proliferation rates compared to NSPCs from the corresponding background strain (C57Bl/6). A secreted factor, identified as cystatin C, was found to be responsible for this effect. Levels of cystatin C were higher in the Tg2576 conditioned medium and lower in the APP-KO conditioned medium. Furthermore, immunodepletion of cystatin C from the conditioned medium completely removed the ability of the conditioned medium to increase NSPC proliferation. The results demonstrate that APP expression stimulates NSPC proliferation, and that this effect is mediated via an increase in cystatin C secretion.

Item Details

Item Type:Refereed Article
Keywords:amyloid precursor protein, neural stem cell, proliferation, neurogenesis, cystatin C, amyloid
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Hu, Y (Ms Ivy Hu)
Author:Hung, AC (Dr Amos Hung)
Author:Cui, H (Mr Hao Cui)
Author:Dawkins, E (Dr Edgar Dawkins)
Author:Bolos, M (Dr Marta Bolos Jurado)
Author:Foa, L (Associate Professor Lisa Foa)
Author:Young, KM (Dr Kaylene Young)
Author:Small, DH (Professor David Small)
ID Code:85208
Year Published:2013
Funding Support:National Health and Medical Research Council (1030939)
Web of Science® Times Cited:11
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-06-18
Last Modified:2017-11-06
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