Possible mechanisms of APP-mediated oxidative stress in Alzheimer's disease.
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.
Multhaup
Gerd
G
ZMBH--Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany. g.multhaup@zmbh.uni-heidelberg.de
Scheuermann
Stefan
S
Schlicksupp
Andrea
A
Simons
Andreas
A
Strauss
Markus
M
Kemmling
André
A
Oehler
Christian
C
Cappai
Roberto
R
Pipkorn
Rüdiger
R
Bayer
Thomas A
TA
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003300:Copper / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D017382:Reactive Oxygen Species; D003300:Copper