Cuajungco, Math P.Goldstein, Lee E.Nunomura, AkihikoSmith, Mark A.Lim, James T.Atwood, Craig S.Huang, XudongFarrag, Yasser W.Perry, GeorgeBush, Ashley I.2021-11-232000-05-08Cuajungco, 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.c0001652000021-92581083-351Xhttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37370313Abeta 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.en-USCell BiologyMolecular BiologyBiochemistryJournal Article2021-11-2310.1074/jbc.c000165200