Oxidative stress in brain agingImplications for therapeutics of neurodegenerative diseases

Floyd, Robert A.; Hensley, Kenneth

doi:10.1016/s0197-4580(02)00019-2

Cited by 736 publications

(474 citation statements)

References 118 publications

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“…The physiological concentration of HNE in the plasma is reportedly from 0.3-0.7 μM (164,165) but its concentration can reach as high 10 μM or more in plasma membrane under conditions of oxidative stress (166,167). While HNE is therefore considered as a biomarker of oxidative stress (167,168), it is also implicated in various oxidative stress-related diseases, including atherosclerosis (169), neurodegenerative diseases (170), and fibrosis (171).…”

Section: A Hne: Production Reaction and Eliminationmentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

217

165

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During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

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Section: A Hne: Production Reaction and Eliminationmentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

217

165

View full text Add to dashboard Cite

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“…Antioxidant defences in the brain are, at best, relatively low. Conversely, the brain is rich in prooxidant iron and in unsaturated fatty acids that are particularly vulnerable to peroxidation [50].…”

Section: High Energy Demands Of Neurons Render Them Vulnerable To Ageingmentioning

confidence: 99%

Ageing and the brain

2007

The Journal of Pathology

177

111

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In this review, the evidence for changes in the human brain with ageing at both the macroscopic and microscopic levels is summarized. Loss of neurons is now recognized to be more modest than initial studies suggested and only affects some neuron populations. Accompanying loss of neurons is some reduction in the size of remaining neurons. This reflects a reduced size of dendritic and axonal arborizations. Some of the likely causes of these changes, including free radical damage resulting from a high rate of oxidative metabolism in neurons, glycation and dysregulation of intracellular calcium homeostasis, are discussed. The roles of genes and environmental factors in causing and responding to ageing changes are explored.

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“…Although the mechanisms responsible for age-related functional deteriorations are not well understood, accrual of macromolecular oxidative damage is widely postulated to play a causal role. Indeed, amounts of oxidatively modified proteins, lipids and nucleic acids differentially increase with age in discrete regions of the brain (reviewed by Floyd and Hensley, 2002;Barja, 2004), as do patterns of gene expression suggestive of oxidative stress (Lee et al, 2000). Protein carbonyl content, a measure of protein oxidation, increases with age most rapidly in hippocampus and striatum , regions that are associated with significant losses in function during aging.…”

Section: Introductionmentioning

confidence: 99%

Effects of age and caloric intake on glutathione redox state in different brain regions of C57BL/6 and DBA/2 mice

2007

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The main purpose of the present study was to determine whether specific regions of the mouse brain exhibit different age-related changes in oxidative stress, as indicated by glutathione redox state and the level of protein-glutathionyl mixed disulfides. Comparison of 3-and 21-month-old mice indicated an age-related decrease in the ratio of reduced to oxidized glutathione (GSH:GSSG) as well as a prooxidizing shift in the calculated redox potential (ranging from 6 to 15 mV) in the cortex, hippocampus, striatum and cerebellum, whereas there was little change in the brainstem. This pro-oxidizing shift in redox state was due to a modest decrease in GSH content occurring in all the brain regions examined, and elevations in GSSG amount that were most pronounced in the striatum and cerebellum. The regional changes in glutathione redox state were paralleled by increases in the amounts of protein-mixed disulfides. A reduction of caloric intake by 40% for a short period (7 weeks), implemented in relatively old mice (17 months), increased the GSH:GSSG ratio and redox potential at 19 months in the same brain regions that exhibited age-related decreases. The effects of age and caloric restriction were qualitatively similar in C57BL/6 and DBA/2 mice. However, young DBA/2 mice, which do not show extension of life span in response to long-term caloric restriction, had lower GSH:GSSG ratios and higher protein-mixed disulfides than age-matched C57BL/6 mice. The current findings demonstrate that oxidative stress, as reflected by glutathione redox state, increases in the aging brain in regions linked to age-associated losses of function and neurodegenerative diseases.

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Oxidative stress in brain agingImplications for therapeutics of neurodegenerative diseases

Cited by 736 publications

References 118 publications

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Ageing and the brain

Effects of age and caloric intake on glutathione redox state in different brain regions of C57BL/6 and DBA/2 mice

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