Dopaminergic cell death in Parkinson’s disease: a role of iron?
Loss of midbrain dopaminergic neurons in Parkinson’s disease is associated to hyperoxidation phenomena. In the human substantia nigra, free radicals may be produced in large quantities i.e, during degradation of dopamine, synthesis and accumulation of neuromelanin, through iron, present in high concentrations. Under normal conditions, production of free radicals is compensated by powerful protective enzymes: superoxide dismutase is detected in neurons, and expressed at high levels in those of the substantia nigra; gluthatione peroxidase is exclusively detected in glial cells. A low density of glial cells surround the substantia nigra neurons relatively to other midbrain areas. Thus nigral dopaminergic neurons may be less protected against deleterious action of free radicals. This may explain their preferential susceptibility to oxidative stress. In Parkinson’s disease, an overproduction of free radicals, suggested by the increased level of lipid peroxidation in the substantia nigra, might accelerate the rate of dopaminergic cells death. Impairment of the oxygen toxicity protective mechanisms may be responsible. Besides, the above normal levels of iron in the substantia nigra may contribute to free radical production and have a role in the toxic process, though one cannot exclude the increased iron content may be a non-specific product of cellular degeneration, a consequence of the gliosis.
KeywordsSubstantia Nigra Dopaminergic Neuron Ventral Tegmental Area Progressive Supranuclear Palsy Midbrain Dopaminergic Neuron
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