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Damage from free radicals has been demonstrated in susceptible neuronal populations in cases of Alzheimer disease. In this study, we investigated whether iron, a potent source of the highly reactive hydroxyl radical that is generated by the Fenton reaction with H2O2, might contribute to the source of radicals in Alzheimer disease. We found, using a modified(More)
Increasing evidence suggests that oxidative damage to proteins and other macromolecules is a salient feature of the pathology of Alzheimer's disease. Establishing the source of oxidants is key to understanding what role they play in the pathogenesis of Alzheimer's disease, and one way to examine this issue is to determine which oxidants are involved in(More)
Advanced glycation end products are a diverse class of posttranslational modifications, stemming from reactive aldehyde reactions, that have been implicated in the pathogenesis of a number of degenerative diseases. Because advanced glycation end products are accelerated by, and result in formation of, oxygen-derived free radicals, they represent an(More)
Recent studies have demonstrated oxidative damage is one of the salient features of Alzheimer's disease (AD). In these studies, glycoxidation adduction to and direct oxidation of amino acid side chains have been demonstrated in the lesions and neurons of AD. To address whether lipid damage may also play an important pathogenic role, we raised rabbit(More)
The age-related neurodegenerative diseases exemplified by Alzheimer&hyp;s disease (AD), Lewy body diseases such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington&hyp;s disease are characterized by the deposition of abnormal forms of specific proteins in the brain. Although several factors appear to underlie the pathological(More)
Electrophilic aldehydes, generated from oxidation of polyunsaturated fatty acyl chains under conditions of oxidative stress, bind to proteins and polynucleotides and can lead to cell death. 4-Hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) have been shown here to be toxic to human neuroblastoma cells in culture at low micromolar concentrations. ONE is 4-5(More)
2-Phenyl-2-(1-piperidinyl)propane (PPP), an analog of phencyclidine, was tested for its ability to inactivate cytochrome P450s (P450s) 2B1 and 2B6. PPP inactivated the 7-(benzyloxy)resorufin O-dealkylation activity of liver microsomes obtained from phenobarbital-induced rats with a K(I) of 11 microM. The 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation(More)
During aging long-lived proteins accumulate specific post-translational modifications. One family of modifications, termed Maillard reaction products, are initiated by the condensation between amino groups of proteins and reducing sugars. Protein modification by the Maillard reaction is associated with crosslink formation, decreased protein solubility, and(More)
The pathological presentation of Alzheimer's disease, the leading cause of senile dementia, involves regionalized neuronal death and an accumulation of intracellular and extracellular filamentous protein aggregates that form lesions termed neurofibrillary tangles and senile plaques, respectively. Several independent parameters have been suggested as the(More)
We present the first evidence for carbonyl-related posttranslational modifications of neurofilaments in the neurofibrillary pathology of Alzheimer's disease (AD). Two distinct monoclonal antibodies that consistently labeled neurofibrillary tangles (NFTs), neuropil threads, and granulovacuolar degeneration in sections of AD tissue also labeled the(More)