Oxidative damage in Alzheimer's

Smith, Mark A.; Perry, George; Richey, Peggy L.; Sayre, Lawrence M.; Anderson, Vernon E.; Beal, M. Flint; Kowall, Neil W.

doi:10.1038/382120b0

Cited by 857 publications

(487 citation statements)

References 4 publications

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“…Brain regions show specific changes in this regard, and carbonyl levels correlate well with tangles [273]. Glycation and autoxidative glycosylation products also accumulate in Alzheimer's brains [274].…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,546

982

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Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

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Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,546

982

View full text Add to dashboard Cite

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“…In disease, various modifications of macromolecules such as sugars, lipids, proteins, and nucleic acids, come into play, and it is now well established that neurodegenerative diseases are associated with oxidative imbalance and its sequelae. In the case of AD, many lines of evidence now indicate that ROS induced by redoxactive metals including iron play a pivotal role in pathogenesis [20][21][22][23][24][25][26][27][28][29]. In the following sections, we will discuss the suggested mechanisms of iron in the neuropathology of AD.…”

Section: Introductionmentioning

confidence: 99%

Iron: The Redox-active Center of Oxidative Stress in Alzheimer Disease

et al. 2007

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Although iron is essential in maintaining the function of the central nervous system, it is a potent source of reactive oxygen species. Excessive iron accumulation occurs in many neurodegenerative diseases including Alzheimer disease (AD), Parkinson's disease, and Creutzfeldt-Jakob disease, raising the possibility that oxidative stress is intimately involved in the neurodegenerative process. AD in particular is associated with accumulation of numerous markers of oxidative stress; moreover, oxidative stress has been shown to precede hallmark neuropathological lesions early in the disease process, and such lesions, once present, further accumulate iron, among other markers of oxidative stress. In this review, we discuss the role of iron in the progression of AD.

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“…Disruption of homeostasis of redox-active metals is particularly significant since substantial evidence for increases in oxidative stress parameters exist [67,76,88,[97][98][99]101,113]. Whether the presence of enhanced oxidative events is the cause or the end result of the disease is not certain.…”

Section: Role Of Reactive Oxygen Species In Biological Systemsmentioning

confidence: 99%

Mechanisms by which metals promote events connected to neurodegenerative diseases

Campbell

Smith

Sayre

et al. 2001

Brain Research Bulletin

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Although the exact causative phenomenon responsible for the onset and progression of neurodegenerative disorders is at present unresolved, there are some clues as to the mechanisms underlying these chronic diseases. This review addresses mechanisms by which endogenous or environmental factors, through interaction with redox active metals, may initiate a common cascade of events terminating in neurodegeneration.

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Oxidative damage in Alzheimer's

Cited by 857 publications

References 4 publications

Biochemistry and pathology of radical-mediated protein oxidation

Biochemistry and pathology of radical-mediated protein oxidation

Iron: The Redox-active Center of Oxidative Stress in Alzheimer Disease

Mechanisms by which metals promote events connected to neurodegenerative diseases

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