Homer2 and Homer3 interact with amyloid precursor protein and inhibit Aβ production

The study of Amyloid Precursor Protein (APP) processing has been the focus of considerable interest, since it leads to A beta peptide generation, the main constituent of neuritic plaques found in brains of Alzheimer's disease patients. Therefore, the identification of novel APP binding partners that regulate A beta peptide production represents a pharmaceutical target aiming at reducing A beta pathology. In this study, we provide evidence that Homer2 and Homer3 but not Homer1 proteins interact specifically with APP. Their expression inhibits APP processing and reduces secretion of A beta peptides. In addition, they decrease the levels of cell surface APP and inhibit maturation of APP and beta-secretase (BACE1). The effects of Homer2 and Homer3 on APP trafficking to the cell surface and/or on APP and BACE1 maturation could be part of the mechanism by which the expression of these proteins leads to the significant reduction of A beta peptide production. (C) 2008 Elsevier Inc. All rights reserved.