Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin?

Citation
Rj. Castellani et al., Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin?, FREE RAD B, 26(11-12), 1999, pp. 1508-1512
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN journal
0891-5849 → ACNP
Volume
26
Issue
11-12
Year of publication
1999
Pages
1508 - 1512
Database
ISI
SICI code
0891-5849(199906)26:11-12<1508:IIRIIA>2.0.ZU;2-1
Abstract
One of the most striking features of Alzheimer disease (AD) is an accumulat ion of iron in neurofibrillary tangles and senile plaques. Intriguingly, th is iron is found as both iron (II) and iron (III) and is redox-active. To a ddress the issue of whether such iron participates in redox cycling, it was essential to investigate how iron (II) accumulates, since oxidation of iro n (II) can lead to the generation of reactive oxygen species. To begin to a ddress this issue, here we investigated ceruloplasmin, a key protein involv ed in the regulation of the redox state of iron by converting iron (II) to iron (III). Cases of AD and age-matched controls, obtained at autopsy with similar postmortem intervals, display similar levels of ceruloplasmin immun oreactivity that is mainly confined to neurons. However, in marked contrast , cases of AD show a significant increase in ceruloplasmin within the neuro pil determined by immunoblot analysis of tissue homogenates as well as a ge neralized increased neuropil staining. Together, these findings suggest tha t neuronal induction of ceruloplasmin is feeble in AD, even while there is an increase in tissue ceruloplasmin. Therefore, a failure of neuronal cerul oplasmin to respond to iron may be an important factor that then leads to a n accumulation of redox-active iron in neurons in AD. (C) 1999 Elsevier Sci ence Inc.