Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

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

Tanabe C, Hotoda N, Sasagawa N, Sehara-Fujisawa A, Maruyama K, Ishiura S

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.

Published 4 December 2006 in Biochem Biophys Res Commun, 352(1): 111-7.
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