Proteomic identification of proteins oxidized by Aβ(1-42) in synaptosomes: Implications for Alzheimer's disease

Debra Boyd-Kimball, Alessandra Castegna, Rukhsana Sultana, H. Fai Poon, Robin Petroze, Bert C. Lynn, Jon B. Klein, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

128 Scopus citations


Protein oxidation has been implicated in Alzheimer's disease (AD) and can lead to loss of protein function, abnormal protein turnover, interference with cell cycle, imbalance of cellular redox potential, and eventually cell death. Recent proteomics work in our laboratory has identified specifically oxidized proteins in AD brain such as: creatine kinase BB, glutamine synthase, ubiquitin carboxy-terminal hydrolase L-1, dihydropyrimidase-related protein 2, α-enolase, and heat shock cognate 71, indicating that a number of cellular mechanisms are affected including energy metabolism, excitotoxicity and/or synaptic plasticity, protein turnover, and neuronal communication. Synapse loss is known to be an early pathological event in AD, and incubation of synaptosomes with amyloid beta peptide 1-42 (Aβ 1-42) leads to the formation of protein carbonyls. In order to test the involvement of Aβ(1-42) in the oxidation of proteins in AD brain, we utilized two-dimensional gel electrophoresis, immunochemical detection of protein carbonyls, and mass spectrometry to identify proteins from synaptosomes isolated from Mongolian gerbils. Aβ(1-42) treatment leads to oxidatively modified proteins, consistent with the notion that Aβ(1-42)-induced oxidative stress plays an important role in neurodegeneration in AD brain. In this study, we identified β-actin, glial fibrillary acidic protein, and dihydropyrimidinase-related protein-2 as significantly oxidized in synaptosomes treated with Aβ(1-42). Additionally, H+-transporting two-sector ATPase, syntaxin binding protein 1, glutamate dehydrogenase, γ-actin, and elongation factor Tu were identified as increasingly carbonylated. These results are discussed with respect to their potential involvement in the pathogenesis of AD.

Original languageEnglish
Pages (from-to)206-215
Number of pages10
JournalBrain Research
Issue number2
StatePublished - May 24 2005

Bibliographical note

Funding Information:
This research was supported, in part, by NIH grants to D.A.B. [AG-05119; AG-10836].


  • Alzheimer's disease
  • Amyloid β-peptide (1-42)
  • Amyloid β-peptide (42-1)
  • Oxidative stress
  • Proteomics

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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