Aqueous dissolution of Alzheimer's disease A beta amyloid deposits by biometal depletion

Citation
Ra. Cherny et al., Aqueous dissolution of Alzheimer's disease A beta amyloid deposits by biometal depletion, J BIOL CHEM, 274(33), 1999, pp. 23223-23228
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
274
Issue
33
Year of publication
1999
Pages
23223 - 23228
Database
ISI
SICI code
0021-9258(19990813)274:33<23223:ADOADA>2.0.ZU;2-#
Abstract
Zn(II) and Cu(II) precipitate AP in vitro into insoluble aggregates that ar e dissolved by metal chelators. We now report evidence that these biometals also mediate the deposition of AP amyloid in Alzheimer's disease, since th e solubilization of AP from post-mortem brain tissue was significantly incr eased by the presence of chelators, EGTA, N,N,N',N'-tetrakis(2-pyridyl-meth yl) ethylene diamine, and bathocuproine. Efficient extraction of A beta als o required Mg(II) and Ca(II), The chelators were more effective in extracti ng AP from Alzheimer's disease brain tissue than age-matched controls, sugg esting that metal ions differentiate the chemical architecture of amyloid i n Alzheimer's disease. Agents that specifically chelate copper and zinc ion s but preserve Mg(II) and Ca(II) may be of therapeutic value in Alzheimer's disease.