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Wild K, August A, Pietrzik CU, et al. Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments. Front Mol Neurosci. 2017;10:21doi: 10.3389/fnmol.2017.00021.
Wild, K., August, A., Pietrzik, C. U., & Kins, S. (2017). Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments. Frontiers in molecular neuroscience, 1021. https://doi.org/10.3389/fnmol.2017.00021
Wild, Klemens, et al. "Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments." Frontiers in molecular neuroscience vol. 10 (2017): 21. doi: https://doi.org/10.3389/fnmol.2017.00021
Wild K, August A, Pietrzik CU, Kins S. Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments. Front Mol Neurosci. 2017 Jan 31;10:21. doi: 10.3389/fnmol.2017.00021. eCollection 2017. PMID: 28197076; PMCID: PMC5281630.
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Front Mol Neurosci. 2017 Jan 31;10:21. doi: 10.3389/fnmol.2017.00021. eCollection 2017.

Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments.

Frontiers in molecular neuroscience

Klemens Wild, Alexander August, Claus U Pietrzik, Stefan Kins

Affiliations

  1. Heidelberg University Biochemistry Center (BZH), University of Heidelberg Heidelberg, Germany.
  2. Division of Human Biology and Human Genetics, Technical University of Kaiserslautern Kaiserslautern, Germany.
  3. Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University Mainz Mainz, Germany.

PMID: 28197076 PMCID: PMC5281630 DOI: 10.3389/fnmol.2017.00021

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.

Keywords: Alzheimer’s disease; amyloid precursor protein (APP); copper; synaptic transmission; zinc

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