title: Structure and functions of the human amyloid precursor protein: the whole is more than the sum of its parts.
abstract: The amyloid precursor protein (APP) is a transmembrane protein that plays major roles in the regulation of several important cellular functions, especially in the nervous system, where it is involved in synaptogenesis and synaptic plasticity. The secreted extracellular domain of APP, sAPPalpha, acts as a growth factor for many types of cells and promotes neuritogenesis in post-mitotic neurons. Alternative proteolytic processing of APP releases potentially neurotoxic species, including the amyloid-beta (Abeta) peptide that is centrally implicated in the pathogenesis of Alzheimer's disease (AD). Reinforcing this biochemical link to neuronal dysfunction and neurodegeneration, APP is also genetically linked to AD. In this review, we discuss the biological functions of APP in the context of tissue morphogenesis and restructuring, where APP appears to play significant roles both as a contact receptor and as a diffusible factor. Structural investigation of APP, which is necessary for a deeper understanding of its roles at a molecular level, has also been advancing rapidly. We summarize recent progress in the determination of the structure of isolated APP fragments and of the conformations of full-length sAPPalpha, in both monomeric and dimeric states. The potential role of APP dimerization for the regulation of its biological functions is also discussed.
authors.affiliation: Instituto de Bioquímica Médica, Programa de Bioquímica e Biofísica Celular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil. mgralle@gwdg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Gralle
authors.forename: Sérgio T
authors.initials: ST
authors.lastname: Ferreira
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D006801:Humans; D017434:Protein Structure, Tertiary
chemical_list: D016564:Amyloid beta-Protein Precursor