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Oxidative damage, including modification of nucleic acids, may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson's disease (PD). To investigate the extent and distribution of nucleic acid oxidative damage in these vulnerable dopaminergic neurons, we immunohistochemically characterized a common product of(More)
Oxidative stress is believed to be an important factor in the development of age-related neurodegenerative diseases such as Alzheimer's disease (AD). The CNS is enriched in polyunsaturated fatty acids and is therefore particularly vulnerable to lipid peroxidation. Indeed, accumulation of lipid peroxidation products has been demonstrated in affected regions(More)
Aged homozygous apolipoprotein E gene-deficient (apoE -/-) mice have been proposed as an experimental model for the role of human apoE isoforms in Alzheimer's disease (AD). However, results from different laboratories have been in conflict regarding the presence or absence of neurodegeneration in these mice. Moreover, despite apoE being the major lipid(More)
Brainstem Lewy bodies (LB) are neuronal inclusions that are closely related to Parkinson's disease (PD). The filamentous component of LB from patients with PD contains biochemically altered neurofilaments (NF). Herein we have tested the hypothesis that the oxidized products of catechols may covalently crosslink NF. Neurofilaments were incubated in the(More)
• Courses and projects that actively involve them in their own education and enhance their ability to formulate and solve real-world design and research problems • A broad education outside of engineering and science that emphasizes the role of electrical and computer engineering in society and builds the leadership skills necessary to deal with the(More)
The neurotoxicity of N,N-diethyldithiocarbamate (DEDC) is established, although the mechanisms responsible for its neurotoxicity are not. Previous experiments have demonstrated that DEDC has the ability to produce CS2-mediated protein cross-linking in vitro and that DEDC releases CS2 in vivo. The release of CS2 with subsequent cross-linking of proteins(More)
A destructive cycle of oxidative stress and mitochondrial dysfunction is proposed in neurodegenerative disease. Lipid peroxidation, one outcome of oxidative challenge, can lead to the formation of 4-hydroxy-2(E)-nonenal (HNE), a lipophilic alkenal that forms stable adducts on mitochondrial proteins. In this study, we characterized the effects of HNE on(More)
An hypothesis is presented which attempts to relate the pathogenesis of both manganese neurotoxicity and Parkinson's disease to cytotoxicity from products of catecholamine oxidation. These include the products resulting from the partial reduction of oxygen (superoxide anion, hydroxyl radical, and hydrogen peroxide) and the semiquinones and ortho quinones(More)
Progression of Parkinson's disease has been associated with several biochemical changes in the substantia nigra including increased oxidative challenge, catechol oxidation, and inhibition of mitochondrial complex I activity. Cysteinylcatechols, formed by nucleophilic addition of cysteine to oxidized catechols, have been identified as markers of catechol(More)
Chronic exposure to acrylamide leads to a dying-back axonopathy afflicting the longest axons of all tested mammalian and avian species. Prior to the onset of acrylamide-induced axonal degeneration, alterations in axonal fast transport have been consistently reported to be more severe for the retrograde than the anterograde direction. The putative retrograde(More)