12,000

We have over 12,000 students, from over 100 countries, within one of the safest campuses in the UK

93%

93% of Lancaster students go into work or further study within six months of graduating

Home > Research > Publications & Outputs > Formation of hydrogen peroxide and hydroxyl rad...
View graph of relations

« Back

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.

Research output: Contribution to journalJournal article

Published

Journal publication date1/06/2002
JournalFree Radical Biology and Medicine
Journal number11
Volume32
Number of pages8
Pages1076-1083
Original languageEnglish

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.