Oxidative stress in synaptosomal proteins from mutant presenilin-1 knock-in mice: Implications for familial Alzheimer's disease

M. A. LaFontaine, M. P. Mattson, D. A. Butterfield

Research output: Contribution to journalArticlepeer-review

Abstract

Presenilin-1 (PS-1) is a transmembrane protein that may be involved in the processing of amyloid precursor protein (APP). Mutations in PS-1 are the major cause of familial Alzheimer's disease (AD). AD brain is under significant oxidative stress, including protein oxidation. In the present study, protein oxidation was compared in synaptosomes from knock-in mice expressing mutant human PS-1 (M146V mutation) and from wild-type mice expressing non-mutant human PS-1. Synaptosomal membrane protein conformational alterations associated with oxidative stress were measured using electron paramagnetic resonance (EPR) in conjunction with a protein-specific spin-label. Direct synaptosomal protein oxidation was assessed by a carbonyl detection assay. Synaptosomal proteins from PS-1 mutant mice displayed increased oxidative stress as measured by both techniques, compared with synaptosomal proteins from wild type mice. These data suggest that PS-1 mutations cause oxidative alterations in synaptosomal membrane protein structure and oxidative modification of synaptosomal proteins. Our findings suggest that familial AD may be associated with oxidative stress that may play a pivotal role in neuronal dysfunction and death.

Original languageEnglish (US)
Pages (from-to)417-421
Number of pages5
JournalNeurochemical Research
Volume27
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Electron paramagnetic resonance
  • Oxidative stress
  • Presenilin-1
  • Protein carbonyls
  • Reactive oxygen species
  • Synaptosomes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

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