Possible involvement of copper(II) in Alzheimer disease.
The beta-amyloid (Abeta) peptide is a principal component of insoluble amyloid plaques that are characteristic neuropathological features of Alzheimer disease (AD). The amyloid peptide also exists as a normal soluble protein that undergoes a pathogenic transition to an aggregated, fibrous form. This transition can be affected by extraneous proteinaceous elements and nonproteinaceous elements such as copper ions, which may promote aggregation and/or stabilization of the fibrils. Copper has been found in abnormally high concentrations in amyloid plaques and AD-affected neuropil, and copper-selective chelators have been shown to dissolve Abeta peptide from postmortem brain specimens. Although Cu(2+) is an essential element for life and the function of numerous enzymes is basic to neurobiology, free or incorrectly bound Cu(2+) can also catalyze generation of the most damaging radicals, such as hydroxyl radical, giving a chemical modification of the protein, alternations in protein structure and solubility, and oxidative damage to surrounding tissue.
Kowalik-Jankowska
Teresa
T
Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland. Terkow@wchuwr.chem.uni.wroc.pl
Ruta-Dolejsz
Monika
M
Wisniewska
Kornelia
K
Lankiewicz
Leszek
L
Kozlowski
Henryk
H
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002449:Cell Aggregation; D002614:Chelating Agents; D003300:Copper / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D017665:Hydroxyl Radical / Q000009:adverse effects; D007477:Ions; D018384:Oxidative Stress; D010446:Peptide Fragments; D058225:Plaque, Amyloid / Q000187:drug effects*; D012307:Risk Factors; D012995:Solubility
D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D007477:Ions; D010446:Peptide Fragments; D017665:Hydroxyl Radical; D003300:Copper