β-Amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate uptake in cultured astrocytes: Implications for alzheimer’s disease

Marni E. Harris, John M. Carney, Pamela S. Cole, Kenneth Hensley, Beverly J. Howard, Laura Martin, Paul Bummer, Yaning Wang, Norman W. Pedigo, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

β -Amyloid (Aβ), the central constituent of senile plaques in Alzheimer’s disease (AD) brains, was shown by us recently to generate free radicals in an oxygen dependent mechanism. Aβ -derived free radicals were detected directly using electron paramagnetic resonance (EPR) spin trapping techniques employing the spin trap phenyl-Q-tert-butylnitrone (PBN). We have extended these studies to investigate the nature of the oxyradicals derived from Aβ peptides, and we show that these free radicals are able to inhibit glutamate uptake in cultured astrocytes. An implication of inhibited astrocyte glutamate uptake in brain is increased extracellular levels of glutamate, which is excitotoxic to neurons. These results support the hypothesis that Aβ neurotoxicity in AD may be due in part to Aβ-derived, oxygen-dependent free radical inhibition of glutamate uptake.

Original languageEnglish
Pages (from-to)1875-1879
Number of pages5
JournalNeuroReport
Volume6
Issue number14
DOIs
StatePublished - Oct 1995

Keywords

  • Alzheimer’s disease
  • Circular dichroism
  • EPR spin trapping
  • Excitotoxicity
  • Glutamate uptake
  • Oxyradicals

ASJC Scopus subject areas

  • Neuroscience (all)

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