The neurotoxic component in Parkinson’s disease may involve iron-melanin interaction and lipid peroxidation in the substantia nigra

  • M. B. H. Youdim
  • D. Ben-Shachar
Part of the New Vistas in Drug Research book series (DRUG RESEARCH, volume 1)


There are indications of oxidative stress in Parkinson’s disease (PD). This can be attributed to the selective increases of iron (III) due to its decompartmentalization and lipid peroxidation and a decrease of glutathione (GSH) oxidation in substantia nigra (SN). The net effect would be accumulation of H2O2, and the formation of free cytotoxic hydroxyl (OH·) radical from the interaction of iron either with H2O2 or melanin or both, to drive the Fenton reaction. Identification of two high-affinity binding sites for Fe3+ on dopamine-melanin indicates the iron binding potency of melanin. This interaction does not result in prevention but rather in potentiation of iron-induced lipid peroxidation, a process selectively inhibited by iron chelators. Thus, H2O2 and melanin are thought to participate in altering the redox state of iron between its two valencies with resultant formation of OH·. This hypothesis can explain the vulnerability and selectivity of melaninized nigrostriatal dopamine neurons to degeneration in PD. Determination of OH· or lipofusin in the CSF, as a by-product of lipid peroxidation, may be a valid approach to early diagnosis of PD.


Lipid Peroxidation Substantia Nigra Iron Overload Oxygen Free Radical Iron Chelator 
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Copyright information

© Springer-Verlag/Wien 1990

Authors and Affiliations

  • M. B. H. Youdim
    • 1
  • D. Ben-Shachar
    • 1
  1. 1.Department of Pharmacology, TechnionRappaport Family Research InstituteHaifaIsrael

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