Mechanisms of MPP+ Neurotoxicity: Oxyradical and Mitochondrial Inhibition Hypotheses
Recent studies demonstrate that 1-methyl-4-phenylpyridinium (MPP+) is selectively toxic to dopaminergic (DA) neurons. Investigations suggest that this selectivity results primarily from the affinity of MPP+ for the dopamine reuptake system which results in preferential accumulation of the toxin within the terminals of the nigrostriatal dopaminergic (DA) system (Javitch and Snyder, 1985;Pileblad and Carlssen, 1985; Mayer et al. 1986).
KeywordsTyrosine Hydroxylase Energy Failure Striatal Slice Gradual Leakage National Parkinson Foundation
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- Hollinden GE, Sanchez-Ramos JR, Sick TJ, and Rosenthal M. MPP+ increases extracellular potassium in rat striatal slices: preliminary evidence that consequences of MPP+ neurotoxicity are spread beyond dopaminergic terminals. Neurosci. Abst. 113; 1502, 1987Google Scholar
- Javitch J A and Snyder SH: Uptake of MPP+ by dopaminergic neurons explains selectivity of parkinsonism inducing neurotoxin MPTP. Europ. J. Pharmacol. 106: 455–56, 1984Google Scholar
- Jellinger K. The pathology of Parkinsonism. In: Movement Disorders. Marsden CD, Fahn S. (eds) Butterworth, Boston 124–150, 1987Google Scholar
- Kopin IJ. Toxins and Parkinson’s Disease: MPTP Parkinsonism in Humans and Animals. In Advances in Neurology Vol 45: Raven Press, NY. 137–144, 1986.Google Scholar
- Mayes PA. Biological Oxidation. In, Review of Physiological Chemistry. Eds., Harper HA, Rodwell VW, Mayes PA. Lange, Chicago, 266–284, 1979Google Scholar
- Sanchez-Ramos JR, Michel P, Weiner WJ, and Hefti F. Selective destruction of cultured dopaminergic neurons from embryonic rat mesencehalon: cytochemical and morphological evidence. J. Neurochem. (in press, 1988a)Google Scholar