Proteomic analysis of brain proteins in APP/PS-1 human double mutant knock-in mice with increasing amyloid β-peptide deposition: Insights into the effects of in vivo treatment with N-acetylcysteine as a potential therapeutic intervention in mild cognitive impairment and Alzheimer's disease

Renã A.S. Robinson, Gururaj Joshi, Quanzhen Huang, Rukhsana Sultana, Austin S. Baker, Jian Cai, William Pierce, Daret K. St. Clair, William R. Markesbery, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Proteomics analyses were performed on the brains of wild-type (WT) controls and an Alzheimer's disease (AD) mouse model, APP/PS-1 human double mutant knock-in mice. Mice were given either drinking water or water supplemented with N-acetylcysteine (NAC) (2 mg/kg body weight) for a period of five months. The time periods of treatment correspond to ages prior to Aβ deposition (i.e. 4-9 months), resembling human mild cognitive impairment (MCI), and after Aβ deposition (i.e. 7-12 months), more closely resembling advancing stages of AD. Substantial differences exist between the proteomes of WT and APP/PS-1 mice at 9 or 12 months, indicating that Aβ deposition and oxidative stress lead to downstreamchanges in protein expression. Altered proteins are involved in energy-related pathways, excitotoxicity, cell cycle signaling, synaptic abnormalities, and cellular defense and structure. Overall, the proteomic results support the notion that NAC may be beneficial for increasing cellular stress responses in WT mice and for influencing the levels of energy-and mitochondria-related proteins in APP/PS-1 mice.

Original languageEnglish
Pages (from-to)4243-4256
Number of pages14
JournalProteomics
Volume11
Issue number21
DOIs
StatePublished - Nov 2011

Keywords

  • APP/PS1
  • Alzheimer disease
  • Animal proteomics
  • Mild cognitive impairment
  • N-acetylcysteine
  • Oxidative stress
  • Protein oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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