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

First Author  Hu Y Year  2013
Journal  J Biol Chem Volume  288
Issue  26 Pages  18853-62
PubMed ID  23671283 Mgi Jnum  J:202777
Mgi Id  MGI:5521437 Doi  10.1074/jbc.M112.443671
Citation  Hu Y, et al. (2013) Role of cystatin C in amyloid precursor protein-induced proliferation of neural stem/progenitor cells. J Biol Chem 288(26):18853-62
abstractText  The amyloid precursor protein (APP) is well studied for its role in Alzheimer 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 knock-out (APP-KO) mice had reduced proliferation rates when compared with 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.
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