부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1471-4159.2005.03616.x Byline: Georgia Agiostratidou (1), Rosa Minana Muros (2), Junichi Shioi, Philippe Marambaud (3), Nikolaos K. Robakis Keywords: Abeta; Alzheimer's disease; E-cadherin; lysosomal/endosomal system; presenilin; [gamma]-secretase Abstract: Abstract The presenilin (PS)/[gamma]-secretase system promotes production of the Abeta (A[beta]) peptides by mediating cleavage of amyloid precursor protein (APP) at the [gamma]-sites. This system is also involved in the processing of type-I transmembrane proteins, including APP, cadherins and Notch1 receptors, at the ϵ-cleavage site, resulting in the production of peptides containing the intracellular domains (ICDs) of the cleaved proteins. Emerging evidence shows that these peptides have important biological functions, raising the possibility that their inhibition by [gamma]-secretase inhibitors may be detrimental to the cell. Here, we show that peptide E-Cad/CTF2, produced by the PS1/[gamma]-secretase processing of E-cadherin, promotes the lysosomal/endosomal degradation of the transmembrane APP derivatives, C99 and C83, and inhibits production of the APP ICD (AICD). In addition, E-Cad/CTF2 decreases accumulation of total secreted A[beta]. These data suggest a novel method to promote the non-amyloidogenic degradation of A[beta] precursors and to inhibit A[beta] production. Article History: Received September 19, 2005; revised manuscript received October 27, 2005; accepted October 28, 2005. Article note: Address correspondence and reprint requests to Nikolaos K. Robakis, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place Box 1229, New York, NY 10029, USA. , E-mail: nikos.robakis@mssm.edu