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

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

Research output: Contribution to journalArticle

163 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 - 15 May 2001
Externally publishedYes

Fingerprint

Synucleins
Hydrogen Peroxide
Parkinson Disease
Lewy Bodies
Spin Trapping
Lewy Body Disease
Peptide Fragments
Gene encoding
Oxidative stress
Inclusion Bodies
Electron Spin Resonance Spectroscopy
Substantia Nigra
Pathologic Processes
Neurodegenerative Diseases
Hydroxyl Radical
Free Radicals
Paramagnetic resonance
In Vitro Techniques
Brain
Oxidative Stress

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

α-synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro. / Turnbull, Stuart; Tabner, Brian J.; Ali El-Agnaf, Omar; Moore, Susan; Davies, Yvonne; Allsop, David.

In: Free Radical Biology and Medicine, Vol. 30, No. 10, 15.05.2001, p. 1163-1170.

Research output: Contribution to journalArticle

Turnbull, Stuart ; Tabner, Brian J. ; Ali El-Agnaf, Omar ; Moore, Susan ; Davies, Yvonne ; Allsop, David. / α-synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro. In: Free Radical Biology and Medicine. 2001 ; Vol. 30, No. 10. pp. 1163-1170.
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