Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 476, Issue 2, Pages 145-151Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2008.03.011
Keywords
Parkinson's disease; neurodegeneration; flavonoid; polyphenol; hesperetin; pelargonidin; quercetin; catechin; caffeic acid; 5-S-cysteinyl-dopamine; DHBT-1; peroxynitrite; brain
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Funding
- Biotechnology and Biological Sciences Research Council [BB/C518222/1] Funding Source: Medline
- Medical Research Council [G0400278/NI02, G0400278] Funding Source: Medline
- MRC [G0400278] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/C518222/1] Funding Source: researchfish
- Medical Research Council [G0400278] Funding Source: researchfish
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Mechanisms of nigral cell injury in Parkinson's disease remain unclear, although a combination of increased oxidative stress, the formation of catecholamine-quinones and the subsequent formation of neurotoxic cysteinyl-catecholamine conjugates may contribute. In the present study, peroxynitrite was observed to generate both 2-S- and 5-S-cysteinyl-dopamine and a dihydrobenzothiazine species, DHBT-1, following the reaction of dopamine with L-cysteine. The formation of 5-S-cysteinyl-dopamine and DHBT-1 in the presence of peroxynitrite induced significant neuronal injury. Pre-treatment of cortical neurons with pelargonidin, quercetin, hesperetin, caffeic acid, the 4'-O-Me derivatives of catechin and epicatechin (0.1-3.0 mu M) resulted in concentration dependant protection against 5-S-cysteinyl-dopamine-induced neurotoxicity. These data suggest that polyphenols may protect against neuronal injury induced by endogenous neurotoxins relevant to the aetiology of the Parkinson disease. (C) 2008 Elsevier Inc. All rights reserved.
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