Archives of Toxicology

, Volume 89, Issue 10, pp 1669–1680 | Cite as

Oxidative stress in Alzheimer disease and mild cognitive impairment: evidence from human data provided by redox proteomics

Review Article

Abstract

Alzheimer disease (AD) is a neurodegenerative disease with many known pathological features, yet there is still much debate into the exact cause and mechanisms for progression of this degenerative disorder. The amyloid-beta (Aβ)-induced oxidative stress hypothesis postulates that it is the oligomeric Aβ that inserts into membrane systems to initiate much of the oxidative stress observed in brain during the progression of the disease. In order to study the effects of oxidative stress on tissue from patients with AD and amnestic mild cognitive impairment (MCI), we have developed a method called redox proteomics that identifies specific brain proteins found to be selectively oxidized. Here, we discuss experimental findings of oxidatively modified proteins involved in three key cellular processes implicated in the pathogenesis of AD progression: energy metabolism, cell signaling and neurotransmission, as well as the proteasomal degradation pathways and antioxidant response systems. These proteomics studies conducted by our laboratory and others in the field shed light on the molecular changes imposed on the cells of AD and MCI brain, through the deregulated increase in oxidative/nitrosative stress inflicted by Aβ and mitochondrial dysfunction.

Keywords

Alzheimer disease Mild cognitive impairment Amyloid-beta Reactive oxygen species Redox proteomics 

Abbreviations

3NT

3-Nitrotyrosine

AD

Alzheimer disease

Amyloid-beta

CRMP2

Collapsin response mediator protein-2

EAD

Early-onset Alzheimer disease

ESI–MS/MS

Electrospray ionization tandem mass spectrometry

FAD

Familial Alzheimer disease

GSH

Glutathione

HNE

4-Hydroxynonenal

IPL

Inferior parietal lobule

LAD

Late-onset Alzheimer disease

MCI

Mild cognitive impairment

NFT

Neurofibrillary tangle

PC

Protein carbonyl

PCAD

Preclinical Alzheimer disease

PET

Positron emission tomography

Pin1

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1

PMI

Postmortem interval

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

SP

Senile plaque

UCH L-1

Ubiquitin carboxy-terminal hydrolase L-1

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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Chemistry and Sanders-Brown Center on AgingUniversity of KentuckyLexingtonUSA

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