Redox proteomics identification of oxidized proteins in Alzheimer's disease hippocampus and cerebellum: An approach to understand pathological and biochemical alterations in AD

Rukhsana Sultana, Debra Boyd-Kimball, H. Fai Poon, Jian Cai, William M. Pierce, Jon B. Klein, Michael Merchant, William R. Markesbery, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

288 Scopus citations

Abstract

Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles, senile plaques and loss of synapses. There is accumulating evidence that oxidative stress plays an important role in AD pathophysiology. Previous redox proteomics studies from our laboratory on AD inferior parietal lobule led to the identification of oxidatively modified proteins that were consistent with biochemical or pathological alterations in AD. The present study was focused on the identification of specific targets of protein oxidation in AD and control hippocampus and cerebellum using a redox proteomics approach. In AD hippocampus, peptidyl prolyl cis-trans isomerase, phosphoglycerate mutase 1, ubiquitin carboxyl terminal hydrolase 1, dihydropyrimidinase related protein-2 (DRP-2), carbonic anhydrase II, triose phosphate isomerase, α-enolase, and γ-SNAP were identified as significantly oxidized protein with reduced enzyme activities relative to control hippocampus. In addition, no significant excessively oxidized protein spots were identified in cerebellum compared to control, consistent with the lack of pathology in this brain region in AD. The identification of oxidatively modified proteins in AD hippocampus was verified by immunochemical means. The identification of common oxidized proteins in different brain regions of AD brain suggests a potential role for these oxidized proteins and thereby oxidative stress in the pathogenesis of Alzheimer's disease.

Original languageEnglish
Pages (from-to)1564-1576
Number of pages13
JournalNeurobiology of Aging
Volume27
Issue number11
DOIs
StatePublished - Nov 2006

Bibliographical note

Funding Information:
The authors thank the University of Kentucky ADRC Clinical and Neuropathology Cores for providing the brain specimens used for this study. This work was supported in part by grants from NIH to D.A.B. [AG-05119; AG-10836], to W.R.M. [5P01-AG0-5119], and to J.B.K. [HL-66358].

Keywords

  • Alzheimer's disease
  • Carbonic anhydrase II
  • Cerebellum
  • Dihydropyrimidinase related protein-2
  • Enolase
  • Hippocampus
  • Peptidyl prolyl cis-trans isomerase
  • Phosphoglycerate mutase 1
  • Protein oxidation
  • Redox proteomics
  • Triose phosphate isomerase
  • Ubiquitin c-terminal hydroxylase 1
  • γ-SNAP

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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