Proteomic identification of proteins specifically oxidized by intracerebral injection of amyloid β-peptide (1-42) into rat brain: Implications for Alzheimer's disease

D. Boyd-Kimball, R. Sultana, H. Fai Poon, B. C. Lynn, F. Casamenti, G. Pepeu, J. B. Klein, D. A. Butterfield

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

Protein oxidation has been shown to result in loss of protein function. There is increasing evidence that protein oxidation plays a role in the pathogenesis of Alzheimer's disease (AD). Amyloid β-peptide (1-42) [Aβ(1-42)] has been implicated as a mediator of oxidative stress in AD. Additionally, Aβ(1-42) has been shown to induce cholinergic dysfunction when injected into rat brain, a finding consistent with cholinergic deficits documented in AD. In this study, we used proteomic techniques to examine the regional in vivo protein oxidation induced by Aβ(1-42) injected into the nucleus basalis magnocellularis (NBM) of rat brain compared with saline-injected control at 7 days post-injection. In the cortex, we identified glutamine synthetase and tubulin β chain 15/α, while, in the NBM, we identified 14-3-3 ζ and chaperonin 60 (HSP60) as significantly oxidized. Extensive oxidation was detected in the hippocampus where we identified 14-3-3 ζ, β-synuclein, pyruvate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate mutase 1. The results of this study suggest that a single injection of Aβ(1-42) into NBM can have profound effects elsewhere in the brain. The results further suggest that Aβ(1-42)-induced oxidative stress in rat brain mirrors some of those proteins oxidized in AD brain and leads to oxidized proteins, which when inserted into their respective biochemical pathways yields insight into brain dysfunction that can lead to neurodegeneration in AD.

Original languageEnglish
Pages (from-to)313-324
Number of pages12
JournalNeuroscience
Volume132
Issue number2
DOIs
StatePublished - 2005

Bibliographical note

Funding Information:
This work was supported in part by NIH grants to D.A.B. [AG-05119; AG-10836] and by a grant from Cassa di Risparmio di Firenze to F.C.

Keywords

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

ASJC Scopus subject areas

  • General Neuroscience

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