Inhibition of the formation of the neurotoxin 5-S-cysteinyl-dopamine by polyphenols.
The death of nigral neurons in Parkinson's disease is thought to involve the formation of the endogenous neurotoxin, 5-S-cysteinyl-dopamine. In the present study, we show that the polyphenols, (+)-catechin and caffeic acid, which contain a catechol moiety, inhibit tyrosinase-induced formation of 5-S-cysteinyl-dopamine via their capacity to undergo tyrosinase-induced oxidation to yield cysteinyl-polyphenol adducts. In contrast, the inhibition afforded by the flavanone, hesperetin, was not accompanied by the formation of cysteinyl-hesperetin adducts, indicating that it may inhibit via direct interaction with tyrosinase. Whilst the stilbene resveratrol also inhibited 5-S-cysteinyl-dopamine formation, this was accompanied by the formation of dihydrobenzothiazine, a strong neurotoxin. Our data indicate that the inhibitory effects of polyphenols against 5-S-cysteinyl-dopamine formation are structure-dependent and shed further light on the mechanisms by which polyphenols exert protection against neuronal injury relevant to neurodegenerative diseases.
Vauzour
David
D
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, The University of Reading, Whiteknights Campus, Reading RG6 6AP, UK.
Vafeiadou
Katerina
K
Spencer
Jeremy P E
JP
D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D013058:Mass Spectrometry; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D059808:Polyphenols
D005419:Flavonoids; D009498:Neurotoxins; D010636:Phenols; D059808:Polyphenols; C047408:5-S-cysteinyldopamine; D014442:Monophenol Monooxygenase; D004298:Dopamine