α-synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro

Stuart Turnbull, Brian J. Tabner, Omar M.A. El-Agnaf, Susan Moore, Yvonne Davies, David Allsop

Research output: Contribution to journalArticlepeer-review

177 Citations (Scopus)

Abstract

Some rare inherited forms of Parkinson's disease (PD) are due to mutations in the gene encoding a 140-amino acid presynaptic protein called α-synuclein. In PD, and some other related disorders such as dementia with Lewy bodies, α-synuclein accumulates in the brain in the form of fibrillar aggregates, which are found inside the neuronal cytoplasmic inclusions known as Lewy bodies. By means of an electron spin resonance (ESR) spin trapping method, we show here that solutions of full-length α-synuclein, and a synthetic peptide fragment of α-synuclein corresponding to residues 61-95 (the so-called non-Aβ component or NAC), both liberate hydroxyl radicals upon incubation in vitro followed by the addition of Fe(II). We did not observe this property for the related β- and γ-synucleins, which are not found in Lewy bodies, and are not linked genetically to any neurodegenerative disorder. There is abundant evidence for the involvement of free radicals and oxidative stress in the pathogenesis of nigral damage in PD. Our new data suggest that the fundamental molecular mechanism underlying this pathological process could be the production of hydrogen peroxide by α-synuclein.

Original languageEnglish
Pages (from-to)1163-1170
Number of pages8
JournalFree Radical Biology and Medicine
Volume30
Issue number10
DOIs
Publication statusPublished - May 15 2001
Externally publishedYes

Keywords

  • Electron spin resonance spectroscopy
  • Free radicals
  • Hydrogen peroxide
  • Hydroxyl radicals
  • Neurodegeneration
  • Parkinson's disease
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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