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Formation of hydrogen peroxide and hydroxyl radicals from Aβ and α-synuclein as a possible mechanism of cell death in Alzheimer’s disease and Parkinson’s disease.

Tabner, Brian J. and Turnbull, Stuart and El-Agnaf, Omar M. A. and Allsop, David (2002) Formation of hydrogen peroxide and hydroxyl radicals from Aβ and α-synuclein as a possible mechanism of cell death in Alzheimer’s disease and Parkinson’s disease. Free Radical Biology and Medicine, 32 (11). pp. 1076-1083. ISSN 0891-5849

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Abstract

The formation of extracellular or intracellular deposits of amyloid-like protein fibrils is a prominent pathological feature of many different neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). In AD, the β-amyloid peptide (Aβ) accumulates mainly extracellularly at the center of senile plaques, whereas, in PD, the -synuclein protein accumulates within neurons inside the Lewy bodies and Lewy neurites. We have shown recently that solutions of Aβ 1–40, Aβ 1–42, Aβ 25–35, -synuclein and non-Aβ component (NAC; residues 61–95 of -synuclein) all liberate hydroxyl radicals upon incubation in vitro followed by the addition of small amounts of Fe(II). These hydroxyl radicals were readily detected by means of electron spin resonance spectroscopy, employing 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent. Hydroxyl radical formation was inhibited by the inclusion of catalase or metal-chelators during Aβ or -synuclein incubation. Our results suggest that hydrogen peroxide accumulates during the incubation of Aβ or -synuclein, by a metal-dependent mechanism, and that this is subsequently converted to hydroxyl radicals, on addition of Fe (II), by Fenton’s reaction. Consequently, one of the fundamental molecular mechanisms underlying the pathogenesis of cell death in AD and PD, and possibly other neurodegenerative or amyloid diseases, could be the direct production of hydrogen peroxide during formation of the abnormal protein aggregates.

Item Type: Article
Journal or Publication Title: Free Radical Biology and Medicine
Uncontrolled Keywords: Free radicals ; Alzheimer’s disease ; Amyloid ; Hydrogen peroxide ; Neurodegeneration ; Oxidative stress ; Parkinson’s disease
Subjects: Q Science > QH Natural history > QH301 Biology
Departments: Faculty of Science and Technology > Lancaster Environment Centre
Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 8857
Deposited By: Prof David Allsop
Deposited On: 15 May 2008 11:43
Refereed?: Yes
Published?: Published
Last Modified: 09 Apr 2014 22:14
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/8857

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