A spectroscopic study of some of the peptidyl radicals formed following hydroxyl radical attack on β-amyloid and α-synuclein

Brian J. Tabner, Stuart Turnbull, Jenny E. King, Fiona E. Benson, Omar Ali El-Agnaf, David Allsop

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

There is clear evidence implicating oxidative stress in the pathology of many neurodegenerative diseases. Reactive oxygen species (ROS) are the primary mediators of oxidative stress, and hydrogen peroxide, a key ROS, is generated during aggregation of the amyloid proteins associated with some of these diseases. Hydrogen peroxide is catalytically converted to the aggressive hydroxyl radical in the presence of Fe(II) and Cu(I), which renders amyloidogenic proteins such as β-amyloid and α-synuclein (implicated in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively) vulnerable to self-inflicted hydroxyl radical attack. Here, we report some of the peptide-derived radicals, detected by electron spin resonance spectroscopy employing sodium 3,5-dibromo-4-nitrosobenzenesulfonate as a spin-trap, following hydroxyl radical attack on Aβ(1-40), α-synuclein and some other related peptides. Significantly, we found that sufficient hydrogen peroxide was self-generated during the early stages of aggregation of Aβ(1-40) to produce detectable peptidyl radicals, on addition of Fe(II). Our results support the hypothesis that oxidative damage to Aβ (and surrounding molecules) in the brain in AD could be due, at least in part, to the self-generation of ROS. A similar mechanism could operate in PD and some other "protein conformational" disorders.

Original languageEnglish
Pages (from-to)731-739
Number of pages9
JournalFree Radical Research
Volume40
Issue number7
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

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Keywords

  • Alzheimer's disease
  • Electron spin resonance
  • Hydrogen peroxide
  • Hydroxyl radical
  • Parkinson's disease
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry

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