RT Journal Article
SR Electronic
T1 Contribution of the endosomal-lysosomal and proteasomal systems in Amyloid-β Precursor Protein derived fragments processing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 300921
DO 10.1101/300921
A1 Caroline Evrard
A1 Pascal Kienlen-Campard
A1 Rémi Opsomer
A1 Bernadette Tasiaux
A1 Jean-Noël Octave
A1 Luc Buée
A1 Nicolas Sergeant
A1 Valérie Vingtdeux
YR 2018
UL http://biorxiv.org/content/early/2018/04/14/300921.abstract
AB Aβ peptides, the major components of amyloid deposits of Alzheimer’s disease, are released following sequential cleavages by secretases of its precursor named the amyloid precursor protein (APP). In addition to secretases, degradation pathways, in particular the endosomal/lysosomal and proteasomal systems have also been reported to contribute to APP processing. However, the respective role of each of these pathways towards APP metabolism remains to be established. To address this, we used HEK 293 cells and primary neurons expressing full-length APPWT or the β-secretase-derived C99 fragments (β-CTFs) in which degradation pathways were selectively blocked using pharmacological drugs. APP metabolites, including carboxy-terminal fragments (CTFs), soluble APP (sAPP) and Aβ peptides were studied. In this report, we show that APP-CTFs produced from endogenous or overexpressed full-length APP are mainly processed by γ-secretase and the endosomal/lysosomal pathway, while in sharp contrast, overexpressed C99 alone is mainly degraded by the proteasome and to a lesser extent by γ-secretase.