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Biochem Biophys Res Commun. 2007 Jan 5;352(1):111-7. Epub 2006 Nov 9.

ADAM19 is tightly associated with constitutive Alzheimer's disease APP alpha-secretase in A172 cells.

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Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.


To elucidate whether new proteases are involved in the processing of amyloid precursor protein (APP), we examined catalytically active ADAM12 and ADAM19 as candidates alpha-secretases. The overexpression of ADAM19 in HEK293 cells resulted in an increase in sAPPalpha. Therefore, we suggest that ADAM19 has a constitutive alpha-secretase activity. We examined regulated alpha-secretase activity by adding phorbol 12-myristate 13-acetate (PMA), but no regulated activity was found. To verify that endogenous ADAM19 has an APP alpha-secretase activity, we examined whether the constitutive level of alpha-secretase activity was reduced by RNA interference with ADAM19 in A172 cells. The amount of secreted sAPPalpha decreased by about 21% following RNAi. These results suggest that ADAM19 has a constitutive alpha-secretase activity for APP.

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