Redox proteomic identification of 4-Hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: Insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease

Tanea Reed, Marzia Perluigi, Rukhsana Sultana, William M. Pierce, Jon B. Klein, Delano M. Turner, Raffaella Coccia, William R. Markesbery, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

Numerous investigations point to the importance of oxidative imbalance in mediating AD pathogenesis. Accumulated evidence indicates that lipid peroxidation is an early event during the evolution of the disease and occurs in patients with mild cognitive impairment (MCI). Because MCI represents a condition of increased risk for Alzheimer's disease (AD), early detection of disease markers is under investigation. Previously we showed that HNE-modified proteins, markers of lipid peroxidation, are elevated in MCI hippocampus and inferior parietal lobule compared to controls. Using a redox proteomic approach, we now report the identity of 11 HNE-modified proteins that had significantly elevated HNE levels in MCI patients compared with controls that span both brain regions: Neuropolypeptide h3, carbonyl reductase (NADPH), α-enolase, lactate dehydrogenase B, phosphoglycerate kinase, heat shock protein 70, ATP synthase α chain, pyruvate kinase, actin, elongation factor Tu, and translation initiation factor α. The enzyme activities of lactate dehydrogenase, ATP synthase, and pyruvate kinase were decreased in MCI subjects compared with controls, suggesting a direct correlation between oxidative damage and impaired enzyme activity. We suggest that impairment of target proteins through the production of HNE adducts leads to protein dysfunction and eventually neuronal death, thus contributing to the biological events that may lead MCI patients to progress to AD.

Original languageEnglish
Pages (from-to)107-120
Number of pages14
JournalNeurobiology of Disease
Volume30
Issue number1
DOIs
StatePublished - Apr 2008

Bibliographical note

Funding Information:
The authors thank the University of Kentucky Alzheimer's Disease Center Core Facility for providing the brain specimens used for this study. This work was supported in part by grants from NIH to DAB: [AG-05119; AG-10836] and to W.R.M. [AG-05119; AG-0288383] and the Abercrombie Foundation to W.R.M.

Keywords

  • 4-hydroxynonenal
  • Alzheimer's disease
  • HNE
  • Lipid peroxidation
  • Mild cognitive impairment
  • Redox proteomics

ASJC Scopus subject areas

  • Neurology

Fingerprint

Dive into the research topics of 'Redox proteomic identification of 4-Hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: Insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this