Methamphetamine and MPTP: Similarities and Differences in Mechanisms of Neurotoxic Action
The primary pathophysiological finding in the brains of those afflicted with Parkinson's Disease (PD) is an extensive loss of nigrostriatal dopaminergic neurons within the basal ganglia. Although considerable research has focused on the elucidation of the cause for this neurodegeneration, the substance or mechanism responsible for this neurodegeneration is unknown. A Parkinsonian syndrome can occur in individuals who are exposed acutely to low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; Ballard et al., 1985) or to those exposed chronically to manganese (e.g. manganese miners; see Barbeau, 1984). The symptoms seen in those patients who have ingested toxic quantities of MPTP are nearly identical to those seen in idiopathic PD whereas those seen in humans who have been exposed chronically to high levels of manganese are somewhat different than those in idiopathic PD and may reflect damage not only to nigrostriatal dopaminergic but to other neuronal systems as well. These findings have led to two different hypotheses regarding the etiology of PD. One is that a compound similar in structure or biochemical characteristics to MPTP, derived from exogenous or endogenous sources, is responsible for the neurodegeneration of nigrostriatal dopaminergic neurons in PD. Another is that the oxidation of DA results in the formation of oxygen-derived reactive species (quinones and/or superoxide or the hydroxyl radical) capable of cytotoxicity as is believed to occur in Mn2+ poisoning.
KeywordsDopaminergic Neuron Neurotoxic Action Tyrosine Hydroxylase Activity Nigrostriatal Dopaminergic Neuron Dopaminergic Neurotoxicity
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