Selectivity of melaninized nigra-striatal dopamine neurons to degeneration in Parkinson's disease may depend on iron-melanin interaction.
The recent studies on the chemical pathology of Parkinson's disease show selective increases of iron and lipid peroxidation and decreased glutathione (GSH) oxidizing capacity in the substantia nigra (SN). These changes are indicative of oxidative stress, possibly due to the accumulation of iron in the SN. It is the melaninized dopamine neurons that are vunerable to degeneration. The investigation of the interaction of iron with dopamine melanin demonstrates the presence of two relatively high affinity binding sites for 59Fe3+ on dopamine melanin. Interaction of Fe3+ with dopamine melanin results in potentiation of lipid peroxidation of rat cerebral cortex as compared to that induced by Fe3+. Only compounds with the ability to chelate iron are able to inhibit the binding of Fe3+ to melanin and the resultant lipid peroxidation. Therapeutic use of iron chelators, with the ability of crossing the blood brain barrier, as agents for retarding the oxidative stress and Parkinson's disease is envisaged.
Rappaport Family Research Institute, Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel.
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Ben-Shachar
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Youdim
D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology
D008543:Melanins; D007501:Iron; D004298:Dopamine