Abstract
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).
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References
Bannon MJ, Goedert M, Williams B. The possible relation of glutathione, melanin and MPTP to Parkinson’s disease. Biochem. Pharmacol. 33: 2697–2698, 1984
DiMonte, D, Sandy MS, Ekstrom G and Smith MT. Comparative studies on the mechanisms of paraquat and MPP + cytotoxicity. Biochem. Biophys. Res. Com. 137: 303–309, 1986
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, 1987
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, 1984
Jellinger K. The pathology of Parkinsonism. In: Movement Disorders. Marsden CD, Fahn S. (eds) Butterworth, Boston 124–150, 1987
Kaufman LM and Barrett JN. Serum factor supporting long term survival of rat central neurons in culture. Science 220:13941396, 1983
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.
LaManna LC, Pikarsky SM, Sick TJ, Rosenthal M. A rapid scanning spectrophotometer designed for biological tissues in vitro or in vivo. Anal. Biochem. 144:483–493,1985
Mayer RA, Kindt MV, Heikkila RE, Prevention of the nigiostriatal toxicity of MPTP by inhibitors of 3,4 dihyd-roxyphenylethylamine transport. J of Neurochem. 47:1073–1079, 1986
Mayes PA. Biological Oxidation. In, Review of Physiological Chemistry. Eds., Harper HA, Rodwell VW, Mayes PA. Lange, Chicago, 266–284, 1979
Nicklas WJ, Vyas I and Heikkila RE. Inhibition of NADH-linked oxidation in brain mitochondria by MPP+, a metabolite of the neurotoxin MPTP. Life Sci. 36:2503–2508, 1985
Perry TL, Yong VW, Jones K, Wright JM. Manipulation of glutathione contents fails to alter dopaminergic nigiostriatal neurotoxicity of MPTP in the mouse. Neurosci. Lett. 70: 261–265, 1986
Pikarsky SM, LaManna JC, Sick TJ, Rosenthal M. A computer assisted rapid-scanning spectrophotometer with applications to tissues in vitro and in vivo. Comp. Biomed. Res. 18: 408–421, 1985
Pileblad E, and Carlsson A: catecholam¡ne-uptake inhibitors prevent the neurotoxicity of MPTP in the mouse brain. Neuropharmacol 24: 689–92, 1985
Ramsay RR, Salach JI, Singer TP. Uptake of the neurotoxin MPP+ by mitochondria and its relation to the inhibition of the mitochondrial oxidatin of NAD +-linkedjsubstrates by MPP+. Biochem. Biophys. Res. Com. 134:743–748, 1986a
Ramsay RR, Salach JI, Dadgar J, Singer TP. Inhibition of mitochondrial NADH dehydrogenase by pyridine derivatives and its possible relation to experimental and idiopathic parkinsonism. Biochem. Biophys. Res. Com. 135:269–275,1986
Sanchez-Ramos JR, Barrett, JN, Goldstein M, Weiner WJ, and Hefti F. MPP+, but not MPTP selectively destroys dopaminergic neurons in cultures of dissociated rat mesencephalic neurons. Neurosci. Lett. 72: 215*#x2013;220,1986.
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)
Sanchez-Ramos JR, Hollinden GE, Sick TJ, Rosenthal M. 1-methyl-4phenylpyridinium (MPP+) increases oxidation of cytochrome b in rat striatal slices. Brain Research 443:183–189, 1988b
Sershen H, Reith ME A, Hashim A and Lajtha A. Protection against MPTP neurotoxicity by the antioxidant ascorbic acid. Neuropharmacol. 24: 1257–1259, 1985
Sick TJ, Rosenthal M, LaManna JC, Lutz PL. Brain potassium ion homeostasis during anoxia and metabolic inhibition in the turtle and rat. Amer. J. Physiol. 243: R281–R288, 1982.
Singer TP, Castagnoli N, Ramsay RR and Trevor AJ. Biochemical events in the development of parkinsonism induced by MPTP. J. Neurochem 49: 1–8, 1987
Turrens JF, Alexandre A, Lehninger AL. Ubisemiquinone is the electron donor for superoxide formation by Complex III of heart mitochondria. Arch. Biochem. Biophys. 237:408–414,1985
Vyas I, Heikkila RE and Nicklas WJ. Studies on the neurotoxicity of MPTP: Inhibition of NAD-linked substrate oxidation by its metabolite MPP+. J. Neurochem. 46: 1501–1507, 1986
Wagner Gc, Carelli RM and Jarvis MF. Ascorbic acid reduces the dopamine depletion induced by methamphetamine and MPP+. Neuropharmacol. 25: 559–61, 1986
Yong VW, Perry TL and Krisman AV. Depletion of Glutathione in brainstem of mice caused by MPTP is prevented by anti-oxidant pretreatment. Neurosci. Lett. 63: 56–60, 1986
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© 1988 Plenum Press, New York
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Sanchez-Ramos, J.R., Hefti, F., Hollinden, G.E., Sick, T.J., Rosenthal, M. (1988). Mechanisms of MPP+ Neurotoxicity: Oxyradical and Mitochondrial Inhibition Hypotheses. In: Hefti, F., Weiner, W.J. (eds) Progress in Parkinson Research. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0759-4_18
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DOI: https://doi.org/10.1007/978-1-4613-0759-4_18
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