APP Receptor? To Be or Not To Be

Amyloid precursor protein (APP) and its metabolites play a key role in Alzheimer's disease pathogenesis. The idea that APP may function as a receptor has gained momentum based on its structural similarities to type I transmembrane receptors and the identification of putative APP ligands. We review the recent experimental evidence in support of this notion and discuss how this concept is viewed in the field. Specifically, we focus on the structural and functional characteristics of APP as a cell surface receptor, and on its interaction with adaptors and signaling proteins. We also address the importance of APP function as a receptor in Alzheimer's disease etiology and discuss how this function might be potentially important for the development of novel therapeutic approaches.

TrendsThe difficulty in defining the precise physiological and pathological function(s) of APP lies primarily in its complex proteolytic processing that generates various metabolites.Based on its structural properties and its diverse functions, APP is not only a molecule that serves as the substrate for Alzheimer's disease-associated Aβ peptides but is also a receptor, a cell-adhesion molecule, and a growth factor ligand capable of activating signaling pathways that elicit physiological responses.Portraying APP and its metabolites as ligand/receptor entity may provide us a more meaningful understanding of how APP could play an important role in health and disease.