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

Turnbull, Stuart and Tabner, Brian J. and Moore, Susan and Davies, Yvonne and El-Agnaf, Omar M. A. and Allsop, David (2001) α-synuclein implicated in Parkinson’s disease catalyses the formation of hydrogen peroxide in vitro. Free Radical Biology and Medicine, 30 (10). pp. 1163-1170. ISSN 0891-5849

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Some rare inherited forms of Parkinson’s disease (PD) are due to mutations in the gene encoding a 140-amino acid presynaptic protein called -synuclein. In PD, and some other related disorders such as dementia with Lewy bodies, -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 -synuclein, and a synthetic peptide fragment of -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 -synuclein.

Item Type: Journal Article
Journal or Publication Title: Free Radical Biology and Medicine
Uncontrolled Keywords: Parkinson’s disease ; Neurodegeneration ; -synuclein ; Hydrogen peroxide ; Hydroxyl radicals ; Electron spin resonance spectroscopy ; Free radicals
Subjects: ?? qh301 ??
Departments: Faculty of Science and Technology > Lancaster Environment Centre
Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 8866
Deposited By: Prof David Allsop
Deposited On: 15 May 2008 11:42
Refereed?: Yes
Published?: Published
Last Modified: 10 Apr 2018 12:12
Identification Number:

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