| Literature DB >> 10438495 |
R A Cherny1, J T Legg, C A McLean, D P Fairlie, X Huang, C S Atwood, K Beyreuther, R E Tanzi, C L Masters, A I Bush.
Abstract
Zn(II) and Cu(II) precipitate Abeta in vitro into insoluble aggregates that are dissolved by metal chelators. We now report evidence that these biometals also mediate the deposition of Abeta amyloid in Alzheimer's disease, since the solubilization of Abeta from post-mortem brain tissue was significantly increased by the presence of chelators, EGTA, N,N,N',N'-tetrakis(2-pyridyl-methyl) ethylene diamine, and bathocuproine. Efficient extraction of Abeta also required Mg(II) and Ca(II). The chelators were more effective in extracting Abeta from Alzheimer's disease brain tissue than age-matched controls, suggesting that metal ions differentiate the chemical architecture of amyloid in Alzheimer's disease. Agents that specifically chelate copper and zinc ions but preserve Mg(II) and Ca(II) may be of therapeutic value in Alzheimer's disease.Entities:
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Year: 1999 PMID： 10438495 DOI： 10.1074/jbc.274.33.23223
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157