Redox proteomics identification of 4-hydroxynonenalmodified brain proteins in Alzheimer's disease: Role of lipid peroxidation in Alzheimer's disease pathogenesis

Marzia Perluigi, Rukhsana Sultana, Giovanna Cenini, Fabio Di Domenico, Maurizio Memo, William M. Pierce, Raffaella Coccia, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

Numerous studies have shown that neuronal lipids are highly susceptible to oxidative stress including in those brain areas directly involved in the neurodegenerative process of Alzheimer's disease (AD). Lipid peroxidation directly damages membranes and also generates a number of secondary biologically active products (toxic aldehydes)that are capable of easily attacking lipids, proteins, and DNA. Accumulating evidence has demonstrated regionally increased brain lipid peroxidation in patients with AD; however, extensive studies on specific targets of lipid peroxidation induced damage are still missing. The present study represents a further step in understanding the relationship between oxidative modification of protein and neuronal death associated with AD. We used a proteomics approach to determine specific targets of lipid peroxidation in AD brain, both in hippocampus and inferior parietal lobule, by coupling immunochemical detection of 4-hydroxynonenal-bound proteins with 2-D polyacrylamide gel electrophoresis and MS analysis. We identified 4-hydroxynonenal-bound proteins in the hippocampus and inferior parietal lobule brain regions of subjects with AD. The identified proteins play different biological functions including energy metabolism, antioxidant system, and structural proteins, thus impairing multiple molecular pathways. Our results provide further evidence for the role of lipid peroxidation in the pathogenesis of AD.

Original languageEnglish
Pages (from-to)682-693
Number of pages12
JournalProteomics - Clinical Applications
Volume3
Issue number6
DOIs
StatePublished - 2009

Keywords

  • 4-Hydroxynonenal
  • Alzheimer's disease
  • Lipid peroxidation
  • Protein oxidation
  • Redox proteomics

ASJC Scopus subject areas

  • Clinical Biochemistry

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