title: Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments.
abstract: Alzheimer's disease (AD) is ultimately linked to the amyloid precursor protein (APP). However, current research reveals an important synaptic function of APP and APP-like proteins (APLP1 and 2). In this context various neurotrophic and neuroprotective functions have been reported for the APP proteolytic fragments sAPPα, sAPPβ and the monomeric amyloid-beta peptide (Aβ). APP is a metalloprotein and binds copper and zinc ions. Synaptic activity correlates with a release of these ions into the synaptic cleft and dysregulation of their homeostasis is linked to different neurodegenerative diseases. Metal binding to APP or its fragments affects its structure and its proteolytic cleavage and therefore its physiological function at the synapse. Here, we summarize the current data supporting this hypothesis and provide a model of how these different mechanisms might be intertwined with each other.
authors.affiliation: Heidelberg University Biochemistry Center (BZH), University of Heidelberg Heidelberg, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Wild
authors.affiliation: Division of Human Biology and Human Genetics, Technical University of Kaiserslautern Kaiserslautern, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: August
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University Mainz Mainz, Germany.
authors.forename: Claus U
authors.initials: CU
authors.lastname: Pietrzik
authors.affiliation: Division of Human Biology and Human Genetics, Technical University of Kaiserslautern Kaiserslautern, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kins
keywords: Alzheimer’s disease; amyloid precursor protein (APP); copper; synaptic transmission; zinc