Reactive oxygen species and Alzheimer's disease.
Although a consensus that Alzheimer's disease (AD) is a single disease has not been reached yet, the involvement of the amyloid precursor protein (APP) and betaA4 (A beta) in the pathologic changes advances our understanding of the underlying molecular alterations. Increasing evidence implicates oxidative stress in the neurodegenerative process of AD. This hypothesis is based on the toxicity of betaA4 in cell cultures, and the findings that aggregation of betaA4 can be induced by metal-catalyzed oxidation and that free oxygen radicals may be involved in APP metabolism. Another neurological disorder, familial amyotrophic lateral sclerosis (FALS), supports our view that AD and FALS may be linked through a common mechanism. In FALS, SOD-Cu(I) complexes are affected by hydrogen peroxide and free radicals are produced. In AD, the reduction of Cu(II) to Cu(I) by APP involves an electron-transfer reaction and could also lead to a production of hydroxyl radicals. Thus, copper-mediated toxicity of APP-Cu(II)/(I) complexes may contribute to neurodegeneration in AD.
Multhaup
G
G
ZMBH-Center for Molecular Biology Heidelberg, University of Heidelberg, Germany. g.multhaup@mail.zmbh.uni-heidelberg.de
Ruppert
T
T
Schlicksupp
A
A
Hesse
L
L
Beher
D
D
Masters
C L
CL
Beyreuther
K
K
D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase