The stabilization of ferrous iron by a toxic beta-amyloid fragment and by an aluminum salt.
Aluminum is a recognized neurotoxin in dialysis encephalopathy and may also be implicated in the etiology of neurodegenerative disease, particularly Alzheimer's disease. Alzheimer's disease is suspected to be associated with oxidative stress, possibly due to the pro-oxidant properties of beta-amyloid present in the senile plaques. The underlying mechanism by which this occurs is not well understood although interactions between amyloid and iron have been proposed. The presence of low molecular weight iron compounds can stimulate free radical production in the brain. This study provides a possible explanation whereby both aluminum and beta-amyloid can potentiate free radical formation by stabilizing iron in its more damaging ferrous (Fe2+) form which can promote the Fenton reaction. The velocity, at which Fe2+ is spontaneously oxidized to Fe3+ at 37 degrees C in 20 mM Bis-Tris buffer at pH 5.8, was significantly slowed in the presence of aluminum salts. A parallel effect of prolongation of stability of soluble ferrous ion, was found in the presence of beta-amyloid fragment (25-35). Ascorbic acid, known to potentiate the pro-oxidant properties of iron, was also capable of markedly stabilizing ferrous ions.
Yang
E Y
EY
Department of Community and Environmental Medicine, University of California, Irvine 92697-1820, USA.
Guo-Ross
S X
SX
Bondy
S C
SC
D000534:Alum Compounds / Q000737:chemistry* / Q000494:pharmacology; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001205:Ascorbic Acid / Q000737:chemistry / Q000494:pharmacology; D001923:Brain Chemistry; D005296:Ferrous Compounds / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology
D000534:Alum Compounds; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D005296:Ferrous Compounds; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C113041:amyloid beta-protein (35-25); C041524:aluminum sulfate; C020748:ferrous sulfate; D001205:Ascorbic Acid