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Furin is an endogenous regulator of alpha-secretase associated APP processing

Cited 43 time in Web of Science Cited 43 time in Scopus
Authors
Hwang, Eun Mi; Kim, Su-Kyoung; Sohn, Ji-Hoon; Lee, Ji-Yeon; Kim, Youngho; Kim, Yong Shik; Mook-Jung, Inhee
Issue Date
2006-09-01
Publisher
Elsevier
Citation
Biochem Biophys Res Commun. 2006 Oct 20;349(2):654-9. Epub 2006 Aug 22.
Keywords
ADAM Proteins/metabolismAlzheimer Disease/metabolismAmyloid Precursor Protein SecretasesAmyloid beta-Protein Precursor/*chemistry/metabolismAnimalsAspartic EndopeptidasesBrain/metabolismCOS CellsCercopithecus aethiopsEndopeptidases/*metabolismFurin/*physiologyGreen Fluorescent Proteins/metabolismHumansMiceMice, Transgenic
Abstract
Constitutive and PKC-regulated alpha-secretase pathways have been reported to produce the secreted form of alpha-secretase-derived APP (sAPPalpha). Here, we examined putative role of furin in the regulation of alpha-secretase activity in vitro and in vivo. Overexpression of the prodomain of furin and infection with a furin-specific inhibitor significantly reduced the levels of sAPPalpha regardless of PKC activity, whereas total APP levels remained unchanged. Furin mRNA levels in the brains of AD patients and Tg2576 mice were significantly lower than those in controls, whereas ADAM10 and TACE mRNA levels were much alike between Tg2576 and littermate mice. Moreover, the injection of furin-adenovirus into Tg2576 mouse brains markedly increased alpha-secretase activity and reduced beta-amyloid protein (Abeta) production in infected brain regions. Our results suggest that furin enhances alpha-secretase activity via the cleavage of ADAM10 and TACE, and that attenuated furin activity is connected to the production of Abeta.
ISSN
0006-291X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16942750

http://hdl.handle.net/10371/22932
DOI
https://doi.org/10.1016/j.bbrc.2006.08.077
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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