Possible mechanisms of APP-mediated oxidative stress in Alzheimer's disease |
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Authors: | Multhaup Gerd Scheuermann Stefan Schlicksupp Andrea Simons Andreas Strauss Markus Kemmling André Oehler Christian Cappai Roberto Pipkorn Rüdiger Bayer Thomas A |
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Affiliation: | ZMBH--Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany. g.multhaup@zmbh.uni-heidelberg.de |
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Abstract: | Oxidative stress was presented to play an important role in the pathogenesis of Alzheimer's disease (AD), especially in the early evolution of AD amyloidogenesis and not only as a consequence thereof. The effect of oxidative stress catalysed by transition metals appears to have a critical relevance in AD. Metal-ion homeostasis is severely dysregulated in AD and it was found that experimentally induced disturbances in the homeostasis of Zn(II) and Cu(II) affect the amyloid precursor protein (APP) metabolism. APP itself binds Zn(II) and Cu(II) at nanomolar concentrations and an altered APP metabolism or expression level is believed to result in neurotoxic processes. |
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