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

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.

authors

Hwang EM,Kim SK,Sohn JH,Lee JY,Kim Y,Kim YS,Mook-Jung I

doi

10.1016/j.bbrc.2006.08.077

subject

Has Abstract

pub_date

2006-10-20 00:00:00

pages

654-9

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)01883-3

journal_volume

349

pub_type

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