Redox-active iron mediates amyloid-beta toxicity

Citation
Ca. Rottkamp et al., Redox-active iron mediates amyloid-beta toxicity, FREE RAD B, 30(4), 2001, pp. 447-450
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN journal
0891-5849 → ACNP
Volume
30
Issue
4
Year of publication
2001
Pages
447 - 450
Database
ISI
SICI code
0891-5849(20010215)30:4<447:RIMAT>2.0.ZU;2-4
Abstract
While amyloid-beta toxicity is mediated by oxidative stress and can be atte nuated by antioxidants, the actual biochemical mechanism underlying neuroto xicity remains to be established. However, since aggregated amyloid-beta ca n interact with transition metals, such as iron, both in vitro and in vivo, we suspected that bound iron might be the mediator of toxicity such that h olo- and apo-amyloid would have differential effects on cellular viability. Here we demonstrate that when amyloid-beta is pretreated with the iron che lator deferoxamine, neuronal toxicity is significantly attenuated while con versely, incubation of holo-amyloid-beta with excess free iron restores tox icity to original levels. These data, taken together with the known sequela e of amyloid-beta, suggest that the toxicity of amyloid-beta is mediated, a t least in part, via redox-active iron that precipitates lipid peroxidation and cellular oxidative stress. (C) 2001 Elsevier Science Inc.