β-amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: Implications to alzheimer′s disease

D. Allan Butterfield, Kenneth Hensley, Marni Harris, Mark Mattson, John Carney

Research output: Contribution to journalArticlepeer-review

409 Scopus citations

Abstract

We have previously reported (Hensley et al., Proc Natl. Acad. Sci USA (1994) in press) that β-amyloid peptide fragments in aqueous media, in a metal-independent reaction, produce reactive peptide free radicals and reactive oxygen species. In contrast to the hours or days necessary to produce neurotoxicity and a detectable free radical for β-amyloid, the extremely neurotoxic Aβ(25-35) fragment of β-amyloid peptide produces a detectable radical in minutes. We now report that Aβ(25-35) is a potent lipoperoxidation initiator, as inferred from peptide-mediated reduction of nitroxyl stearate spin labels bound to rodent neocortical synaptosomal membranes. Aβ(25-35) rapidly quenches the paramagnetism of membrane-bound 12-nitroxyl stearate spin probe deep within the lipid bilayer, but reacts poorly with the 5-nitroxyl isomer whose paramagnetic center is near the lipid/water interface. Aβ(35-25), the non-neurotoxic reverse sequence of Aβ(25-35), shows little proclivity to reduce either spin label. These findings are formulated into a“molecular shrapnel” model of neuronal membrane damage in Alzheimer′s disease.

Original languageEnglish
Pages (from-to)710-715
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume200
Issue number2
DOIs
StatePublished - Apr 29 1994

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'β-amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: Implications to alzheimer′s disease'. Together they form a unique fingerprint.

Cite this