TY - JOUR

T1 - α-synuclein implicated in Parkinson’s disease catalyses the formation of hydrogen peroxide in vitro.

AU - Turnbull, Stuart

AU - Tabner, Brian J.

AU - Moore, Susan

AU - Davies, Yvonne

AU - El-Agnaf, Omar M. A.

AU - Allsop, David

PY - 2001/5/15

Y1 - 2001/5/15

N2 - 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.

AB - 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.

KW - Parkinson’s disease

KW - Neurodegeneration

KW - -synuclein

KW - Hydrogen peroxide

KW - Hydroxyl radicals

KW - Electron spin resonance spectroscopy

KW - Free radicals

U2 - 10.1016/S0891-5849(01)00513-5

DO - 10.1016/S0891-5849(01)00513-5

M3 - Journal article

VL - 30

SP - 1163

EP - 1170

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 10

ER -