TY  - JOUR
A1  - Laßek, Melanie
A1  - Weingarten, Jens
A1  - Wegner, Martin
A1  - Neupärtl, Moritz
A1  - Array, Tabiwang N.
A1  - Harde, Eva
A1  - Beckert, Benedikt
A1  - Golghalyani, Vahid
A1  - Ackermann, Jörg
A1  - Koch, Ina
A1  - Müller, Ulrike C.
A1  - Karas, Michael
A1  - Acker-Palmer, Amparo
A1  - Volknandt, Walter
T1  - APP deletion accounts for age-dependent changes in the bioenergetic metabolism and in hyperphosphorylated CaMKII at stimulated hippocampal presynaptic active zones
T2  - Frontiers in synaptic neuroscience
N2  - Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice.
KW  - aging
KW  - amyloid precursor protein
KW  - hippocampus
KW  - LTP
KW  - mitochondria
KW  - presynaptic active zone
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45156
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-451568
SN  - 1663-3563
N1  - Copyright © 2017 Laßek, Weingarten, Wegner, Neupärtl, Array, Harde, Beckert, Golghalyani, Ackermann, Koch, Müller, Karas, Acker-Palmer and Volknandt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 9
IS  - Art. 1
SP  - 1
EP  - 14
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -