The specific vulnerability of the substantia nigra to MPTP is related to the presence of transition metals.
We demonstrate that the high concentration of transition metals in the substantia nigra could be a major factor responsible for the specificity of cell damage by the Parkinsonism-causing neurotoxin MPTP. It will be shown that these metals in vitro, and MPTP, each potentiate the autoxidation of dopamine and the production of aminochrome through the generation of superoxide, hydroxyl radicals, hydrogen peroxide and reactive semiquinones. Moreover, the same metals contribute to the oxidation of MPTP itself, further enhancing dopamine autoxidation.
Poirier
J
J
Donaldson
J
J
Barbeau
A
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003035:Cobalt / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D005609:Free Radicals; D006801:Humans; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007501:Iron / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
D005609:Free Radicals; D006878:Hydroxides; D008670:Metals; D011725:Pyridines; D017665:Hydroxyl Radical; D003035:Cobalt; D008345:Manganese; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007501:Iron; D013482:Superoxide Dismutase; D015032:Zinc; D004298:Dopamine