Evidence that the β-Amyloid Plaques of Alzheimer's Disease Represent the Redox-silencing and Entombment of Aβ by Zinc
Author
Cuajungco, Math P.
Goldstein, Lee E.
Nunomura, Akihiko
Smith, Mark A.
Lim, James T.
Atwood, Craig S.
Farrag, Yasser W.
Bush, Ashley I.
Published Version
https://doi.org/10.1074/jbc.c000165200Metadata
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Cuajungco, Math P., Lee E. Goldstein, Akihiko Nunomura, Mark A. Smith, James T. Lim, Craig S. Atwood, Xudong Huang et al. "Evidence that the β-Amyloid Plaques of Alzheimer's Disease Represent the Redox-silencing and Entombment of Aβ by Zinc." Journal of Biological Chemistry 275, no. 26 (2000): 19439-19442. DOI: 10.1074/jbc.c000165200Abstract
Abeta binds Zn(2+), Cu(2+), and Fe(3+) in vitro, and these metals are markedly elevated in the neocortex and especially enriched in amyloid plaque deposits of individuals with Alzheimer's disease (AD). Zn(2+) precipitates Abeta in vitro, and Cu(2+) interaction with Abeta promotes its neurotoxicity, correlating with metal reduction and the cell-free generation of H(2)O(2) (Abeta1-42 > Abeta1-40 > ratAbeta1-40). Because Zn(2+) is redox-inert, we studied the possibility that it may play an inhibitory role in H(2)O(2)-mediated Abeta toxicity. In competition to the cytotoxic potentiation caused by coincubation with Cu(2+), Zn(2+) rescued primary cortical and human embryonic kidney 293 cells that were exposed to Abeta1-42, correlating with the effect of Zn(2+) in suppressing Cu(2+)-dependent H(2)O(2) formation from Abeta1-42. Since plaques contain exceptionally high concentrations of Zn(2+), we examined the relationship between oxidation (8-OH guanosine) levels in AD-affected tissue and histological amyloid burden and found a significant negative correlation. These data suggest a protective role for Zn(2+) in AD, where plaques form as the result of a more robust Zn(2+) antioxidant response to the underlying oxidative attack.Other Sources
http://pubmed.ncbi.nlm.nih.gov/10801774/Terms of Use
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https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37370313
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