The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I)
The transition metal ion copper(II) has a critical role in chronic neurologic diseases. The amyloid precursor protein (APP) of Alzheimer's disease or a synthetic peptide representing its copper-binding site reduced bound copper(II) to copper(I). This copper ion-mediated redox reaction led to disulfide bond formation in APP, which indicated that free sulfhydryl groups of APP were involved. Neither superoxide nor hydrogen peroxide had an effect on the kinetics of copper(II) reduction. The reduction of copper(II) to copper(I) by APP involves an electron-transfer reaction and could enhance the production of hydroxyl radicals, which could then attack nearby sites. Thus, copper-mediated toxicity may contribute to neurodegeneration in Alzheimer's disease.
Multhaup
G
G
ZMBH-Center for Molecular Biology Heidelberg, University of Heidelberg, Germany.
Schlicksupp
A
A
Hesse
L
L
Beher
D
D
Ruppert
T
T
Masters
C L
CL
Beyreuther
K
K
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D003300:Copper / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D003553:Cystine / Q000378:metabolism; D004579:Electron Transport; D005290:Ferric Compounds / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D013058:Mass Spectrometry; D009842:Oligopeptides / Q000494:pharmacology; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D005290:Ferric Compounds; D009842:Oligopeptides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D013481:Superoxides; D017665:Hydroxyl Radical; D003553:Cystine; C020905:glycyl-histidyl-lysine; D006639:Histidine; D003300:Copper; D006861:Hydrogen Peroxide; D003545:Cysteine