Mechanism of 6-hydroxydopamine neurotoxicity.
The catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) has recently been found to be formed endogenously in patients suffering from Parkinson's disease. In this article, we highlight the latest findings on the biochemical mechanism of 6-OHDA toxicity. 6-OHDA has two ways of action: it easily forms free radicals and it is a potent inhibitor of the mitochondrial respiratory chain complexes I and IV. The inhibition of respiratory enzymes by 6-OHDA is reversible and insensitive towards radical scavengers and iron chelators with the exception of desferrioxamine. We conclude that free radicals are not involved in the interaction between 6-OHDA and the respiratory chain and that the two mechanisms are biochemically independent, although they may act synergistically in vivo.
Glinka
Y
Y
Department of Pharmacology, Bruce Rappaport Family Research Institute, Faculty of Medicine, Technion, Haifa, Israel.
Gassen
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M
Youdim
M B
MB
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002614:Chelating Agents / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008959:Models, Neurological; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress; D016627:Oxidopamine / Q000378:metabolism / Q000633:toxicity*; D010101:Oxygen Consumption / Q000187:drug effects; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology
D002614:Chelating Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D009498:Neurotoxins; D016627:Oxidopamine