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Oxidative Alterations in Alzheimer's Disease

Published on Apr 5, 2006in Brain Pathology 6.16
· DOI :10.1111/j.1750-3639.1999.tb00215.x
William R. Markesbery109
Estimated H-index: 109
(UK: University of Kentucky),
John M. Carney40
Estimated H-index: 40
Cite
Abstract
There is increasing evidence that free radical damage to brain lipids, carbohydrates, proteins, and DNA is involved in neuron death in neurodegenerative disorders. The largest number of studies have been performed in Alzheimer's disease (AD) where there is considerable support for the oxidative stress hypothesis in the pathogenesis of neuron degeneration. In autopsied brain there is an increase in lipid peroxidation, a decline in polyunsaturated fatty acids (PUFA) and an increase in 4-hydroxynonenal (HNE), a neurotoxic aldehyde product of PUFA oxidation. Increased protein oxidation and a marked decline in oxidative-sensitive enzymes, glutamine synthetase and creatinine kinase, are found in the brain in AD. Increased DNA oxidation, especially 8-hydroxy-2′-deoxyguanosine (8-OHdG) is present in the brain in AD. Immunohistochemical studies show the presence of oxidative stress products in neurofibrillary tangles and senile plaques in AD. Markers of lipid peroxidation (HNE, isoprostanes) and DNA (8-OHdG) are increased in CSF in AD. In addition, inflammatory response markers (the complement cascade, cytokines, acute phase reactants and proteases) are present in the brain in AD. These findings, coupled with epidemiologic studies showing that anti-inflammatory agents slow the progression or delay the onset of AD, suggest that inflammation plays a role in AD. Overall these studies indicate that oxidative stress and the inflammatory cascade, working in concert, are important in the pathogenetic cascade of neurodegeneration in AD, suggesting that therapeutic efforts aimed at both of these mechanisms may be beneficial.
  • References (131)
  • Citations (648)
Cite
References131
Newest
Published on Jun 28, 2008in Journal of Neurochemistry 4.87
Lars Svennerholm63
Estimated H-index: 63
,
Carl-Gerhard Gottfries38
Estimated H-index: 38
: Major membrane lipids were quantified in frontal (Brodmann area 9) and temporal (Brodmann areas 21 and 22) cortices, caudate nucleus, hippocampus, and frontal white matter of 12 cases with Alzheimer's disease (AD) type I (early onset), 21 cases with AD type II (late onset), and 20 age-matched controls. The concentration of gangliosides—a marker for axodendritic arborization—was reduced to 58–70% of the control concentration in all four gray areas (p < 0.0001) and to 81 % in frontal white matte...
Published on Dec 17, 2006in Annals of the New York Academy of Sciences 4.29
Carol A. Colton46
Estimated H-index: 46
(Georgetown University),
Julie Snell6
Estimated H-index: 6
(NIH: National Institutes of Health)
+ 1 AuthorsDaniel L. Gilbert21
Estimated H-index: 21
(NIH: National Institutes of Health)
Published on Nov 23, 2002in Journal of Neurochemistry 4.87
Daniel R. D. Premkumar15
Estimated H-index: 15
,
Mark A. Smith119
Estimated H-index: 119
(Case Western Reserve University)
+ 6 AuthorsRajesh N. Kalaria55
Estimated H-index: 55
(Case Western Reserve University)
Previous studies demonstrated the specific association of heme oxygenase (HO)-1 protein to the neurofibrillary pathology of Alzheimer's disease (AD). In this study, we used reverse transcription-polymerase chain reaction methods to show the increased expression of HO-1 but not HO-2 mRNA transcripts in cerebral cortex and cerebral vessels from subjects with AD compared with age-matched non-AD controls. Neither the HO-1 nor the HO-2 mRNA level was altered in the cerebellum, a brain region usually ...
Published on Nov 23, 2002in Journal of Neurochemistry 4.87
Kenneth Hensley43
Estimated H-index: 43
,
Nathan Hall11
Estimated H-index: 11
+ 9 AuthorsD Allanbutterfield106
Estimated H-index: 106
Abstract: Four biomarkers of neuronal protein oxidation [W/S ratio of MAL-6 spin-labeled synaptosomes, phenylhydrazine-reactive protein carbonyl content, glutamine synthetase (GS) activity, creatine kinase (CK) activity] in three brain regions [cerebellum, inferior parietal lobule (IPL), and hippocampus (HIP)] of Alzheimer's disease (AD)-demented and age-matched control subjects were assessed. These endpoints indicate that AD brain protein may be more oxidized than that of control subjects. The ...
Published on Nov 23, 2002in Journal of Neurochemistry 4.87
M. Kerry O'Banion27
Estimated H-index: 27
,
Janice C. Miller1
Estimated H-index: 1
+ 2 AuthorsPaul D. Coleman45
Estimated H-index: 45
Activation of glial cells and the consequent release of cytokines, proteins, and other intercellular signaling molecules is a well-recognized phenomenon in brain injury and neurodegenerative disease. We and others have previously described an inducible prostaglandin G/H synthase, known as PGHS-2 or cyclooxygenase-2, that is up-regulated in many cell systems by cytokines and growth factors and down-regulated by glucocorticoid hormones. In cultured mouse astrocytes we observed increased production...
Published on Nov 23, 2002in Journal of Neurochemistry 4.87
Elizabeth M. Mutisya2
Estimated H-index: 2
(Harvard University),
Allen C. Bowling10
Estimated H-index: 10
(Harvard University),
M. Flint Beal137
Estimated H-index: 137
(Harvard University)
: A defect in energy metabolism may play a role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease. In the present study, we examined the activities of the enzymes that catalyze oxidative phosphorylation in frontal, temporal, parietal, and occipital cortex from Alzheimer's disease patients and age-matched controls. Complex I and complex II–III activities showed a small decrease in occipital cortex, but were unaffected in the other cortical areas. The most consistent c...
Published on Nov 23, 2002in Journal of Neurochemistry 4.87
Mark P. Mattson177
Estimated H-index: 177
,
Mark A. Lovell62
Estimated H-index: 62
+ 1 AuthorsWilliam R. Markesbery109
Estimated H-index: 109
(UK: University of Kentucky)
Exposure of cultured rat hippocampal neurons to glutamate resulted in accumulation of cellular peroxides (measured using the dye 2,7-dichlorofluorescein). Peroxide accumulation was prevented by an N-methyl-D-aspartate (NMDA) receptor antagonist and by removal of extracellular Ca 2+ , indicating the involvement of NMDA receptor-induced Ca 2+ influx in peroxide accumulation. Glutamate-induced reactive oxygen species contributed to loss of Ca 2+ homeostasis and excitotoxic injury because antioxidan...
Published on Nov 23, 2002in Journal of Neurochemistry 4.87
W. Gsell22
Estimated H-index: 22
(University of Würzburg),
Rudolf Conrad1
Estimated H-index: 1
(University of Würzburg)
+ 8 AuthorsHelmut Beckmann41
Estimated H-index: 41
(University of Würzburg)
: “Oxidative stress” may be of significance in the etiopathogenesis of dementia of Alzheimer type (DAT). Therefore, we measured activities of the enzymes superoxide dismutase (SOD) and catalase (CAT), which detoxicate reactive oxygen species. Enzyme activities were measured postmortem in basal ganglia, cortical, and limbic brain regions of patients with DAT and age-matched controls. SOD activity increased with age in basal nucleus of Meynert. However, there was no significant difference in SOD a...
Published on Nov 18, 2002in Journal of Neurochemistry 4.87
Jeffrey N. Keller58
Estimated H-index: 58
,
Zheng Pang1
Estimated H-index: 1
(UK: University of Kentucky)
+ 4 AuthorsMark P. Mattson177
Estimated H-index: 177
(UK: University of Kentucky)
Abstract: Deposits of amyloid β-peptide (Aβ), reduced glucose uptake into brain cells, oxidative damage to cellular proteins and lipids, and excitotoxic mechanisms have all been suggested to play roles in the neurodegenerative process in Alzheimer's disease. Synapse loss is closely correlated with cognitive impairments in Alzheimer's disease, suggesting that the synapse may be the site at which degenerative mechanisms are initiated and propagated. We report that Aβ causes oxyradical-mediated imp...
Published on Nov 18, 2002in Journal of Neurochemistry 4.87
Emmanuelle M. Blanc9
Estimated H-index: 9
(UK: University of Kentucky),
Jeremiah F. Kelly4
Estimated H-index: 4
+ 2 AuthorsMark P. Mattson177
Estimated H-index: 177
(UK: University of Kentucky)
: Considerable data indicate that oxidative stress and membrane lipid peroxidation contribute to neuronal degeneration in an array of age-related neurodegenerative disorders. In contrast, the impact of subtoxic levels of membrane lipid peroxidation on neuronal function is largely unknown. We now report that 4-hydroxy-nonenal (HNE), an aldehydic product of lipid peroxidation, disrupts coupling of muscarinic cholinergic receptors and metabotropic glutamate receptors to phospholipase C-linked GTP-b...
Cited By648
Newest
Published on Sep 1, 2019in Ageing Research Reviews 10.39
Virginia Boccardi16
Estimated H-index: 16
(University of Perugia),
Ilenia Murasecco (University of Perugia), Patrizia Mecocci68
Estimated H-index: 68
(University of Perugia)
Abstract Alzheimer's disease (AD) is the most prevalent form of dementia, particularly in old age subjects. Hyperinsulinemia and insulin resistance, which are known as pathophysiological features of Type 2 Diabetes Mellitus (T2DM), have also been demonstrated to have a significant impact on cognitive impairment. Studies have shown that an altered insulin pathway may interact with amyloid-β protein deposition and tau protein phosphorylation, both leading factors for AD development. Drugs used for...
Published on Jun 17, 2019in Current Pharmacology Reports
Ava Nasrolahi2
Estimated H-index: 2
(Tabriz University of Medical Sciences),
Javad Mahmoudi9
Estimated H-index: 9
(Tabriz University of Medical Sciences)
+ 3 AuthorsShahram Darabi4
Estimated H-index: 4
(QUMS: Qazvin University of Medical Sciences)
Neurodegeneration is a term for the description of the progressive neuronal and neural structure loss, function, and their populations in the central nervous system (CNS). Recent studies have shed light on shared pathological mechanisms including inflammation, mitochondrial dysfunction, and oxidative stress between diabetes mellitus (DM) and neurodegenerative disorders. The association between these age-related chronic diseases has attracted immense attention during the past decade. Because shar...
Published on Jul 12, 2019
Marco Mellado2
Estimated H-index: 2
(UCV: Pontifical Catholic University of Valparaíso),
Cristian O. Salas10
Estimated H-index: 10
(UC: Pontifical Catholic University of Chile)
+ 4 AuthorsMauricio Cuellar7
Estimated H-index: 7
(Valpo: Valparaiso University)
Published on Jul 1, 2019in Magnetic Resonance Imaging 2.11
Alexandra Badea19
Estimated H-index: 19
(Duke University),
Natalie A Delpratt1
Estimated H-index: 1
(Duke University)
+ 7 AuthorsBrian B. Avants (UVA: University of Virginia)
Abstract To understand multifactorial conditions such as Alzheimer's disease (AD) we need brain signatures that predict the impact of multiple pathologies and their interactions. To help uncover the relationships between pathology affected brain circuits and cognitive markers we have used mouse models that represent, at least in part, the complex interactions altered in AD, while being raised in uniform environments and with known genotype alterations. In particular, we aimed to understand the r...
Published on Jun 28, 2019in Journal of Cellular Physiology 4.52
Huaiqing Luo (CSU: Central South University), Li Han (Changsha Medical University), Jin Xu (Changsha Medical University)
Published on Jun 1, 2019in Journal of Cellular Physiology 4.52
R. Avola17
Estimated H-index: 17
(University of Catania),
Adriana Carol Eleonora Graziano12
Estimated H-index: 12
(University of Catania)
+ 2 AuthorsVenera Cardile33
Estimated H-index: 33
(University of Catania)
Published on May 21, 2019in Journal of Alzheimer's Disease 3.70
Hugo McGurran (UvA: University of Amsterdam), Jordan M Glenn1
Estimated H-index: 1
+ 1 AuthorsNicholas T. Bott7
Estimated H-index: 7
(Palo Alto University)
Published on May 1, 2019in Mitochondrion 3.45
Srinivasu Karri3
Estimated H-index: 3
(University of Hyderabad),
Swati Singh3
Estimated H-index: 3
(University of Hyderabad)
+ 5 AuthorsNaresh Babu V. Sepuri17
Estimated H-index: 17
(University of Hyderabad)
Abstract Perturbations in mitochondrial redox levels oxidize nucleotide exchanger Mge1, compromising its ability to bind to the Hsp70, while the Mxr2 enzyme reduces the oxidized Mge1. However, the effects of persistent oxidative stress on Mge1 structure and function are not known. In this study, we show that oxidation-induced selective and local structural adaptations cause the detachment of Mge1 from Hsp70. Notably, persistent oxidative stress causes monomeric Mge1 to aggregate and to generate ...
Published on Feb 22, 2019in Biological Trace Element Research 2.43
Ercan Babür , B. Tan2
Estimated H-index: 2
+ 3 AuthorsNurcan Dursun10
Estimated H-index: 10
Among the chemical factors that have been implicated in the etiology of dementia, recent concern has focused on both increased and decreased exposure to the metalloid selenium (Se). This report describes the molecular, behavioral, and electrophysiological analysis of rats that were fed with Se-free chow and Se-enriched tap water for 21 days. Three groups were produced, feeding them on a deficient diet with different Selenium content. Hippocampus-dependent spatial learning was measured using the ...