In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: A central role for bound transition metals

Citation
Lm. Sayre et al., In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: A central role for bound transition metals, J NEUROCHEM, 74(1), 2000, pp. 270-279
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
0022-3042 → ACNP
Volume
74
Issue
1
Year of publication
2000
Pages
270 - 279
Database
ISI
SICI code
0022-3042(200001)74:1<270:ISOCBN>2.0.ZU;2-Y
Abstract
There is a great deal of evidence to support a pathogenic role of oxidative stress in Alzheimer's disease (AD), but the sources of reactive oxygen spe cies have not been directly demonstrated. In this study, using a novel in s itu detection system, we show that neurofibrillary tangles and senile plaqu es are major sites for catalytic redox reactivity. Pretreatment with defero xamine or diethylenetriaminepentaacetic acid abolishes the ability of the l esions to catalyze the H2O2-dependent oxidation of 3,3'-diaminobenzidine (D AB), strongly suggesting the involvement of associated transition metal ion s. Indeed, following chelated removal of metals, incubation with iron or co pper salts reestablished lesion-dependent catalytic redox reactivity. Altho ugh DAB oxidation can also detect peroxidase activity, this was inactivated by H2O2 pretreatment before use of DAB, as shown by a specific peroxidase detection method. Model studies confirmed the ability of certain copper and iron coordination complexes to catalyze the H2O2-dependent oxidation of DA B. Also, the microtubule-associated protein tau, as an in vitro model for p roteins relevant to AD pathology, was found capable of adventitious binding of copper and iron in a redox-competent manner. Our findings suggest that neurofibrillary tangles and senile plaques contain redox-active transition metals and may thereby exert prooxidant or possibly antioxidant activities, depending on the balance among cellular reductants and oxidants in the loc al microenvironment.