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The cytoplasmic sequence of E‐cadherin promotes non‐amyloidogenic degradation of Aβ precursors
Author(s) -
Agiostratidou Georgia,
Muros Rosa Miñana,
Shioi Junichi,
Marambaud Philippe,
Robakis Nikolaos K.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03616.x
Subject(s) - amyloid precursor protein , transmembrane protein , presenilin , endosome , microbiology and biotechnology , alpha secretase , peptide , intracellular , chemistry , cadherin , p3 peptide , cleavage (geology) , amyloid precursor protein secretase , transmembrane domain , biochemistry , cytoplasm , receptor , biology , cell , alzheimer's disease , medicine , paleontology , disease , fracture (geology)
The presenilin (PS)/γ‐secretase system promotes production of the Abeta (Aβ) peptides by mediating cleavage of amyloid precursor protein (APP) at the γ‐sites. This system is also involved in the processing of type‐I transmembrane proteins, including APP, cadherins and Notch1 receptors, at the ɛ‐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 γ‐secretase inhibitors may be detrimental to the cell. Here, we show that peptide E‐Cad/CTF2, produced by the PS1/γ‐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 Aβ. These data suggest a novel method to promote the non‐amyloidogenic degradation of Aβ precursors and to inhibit Aβ production.