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MPTP as a Mitochondrial Neurotoxic Model of Parkinson's Disease

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Abstract

1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent neurotoxin extensively used to model Parkinson's disease (PD). A cascade of deleterous events, in which mitochondria play a pivotal role, drives MPTP neurotoxicity. How mitochondria are affected by MPTP and how their defect contributes to the demise of dopaminergic neurons in this model of PD are discussed in this review.

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REFERENCES

  • Aiuchi, T., Shirane, Y., Kinemuchi, H., Arai, Y., Nakaya, K., and Nakamura, Y. (1988). Neurochem. Int. 12, 525–531.

    Google Scholar 

  • Andreassen, O. A., Ferrante, R. J., Dedeoglu, A., Albers, D. W., Klivenyi, P., Carlson, E. J., Epstein, C. J., and Beal, M. F. (2001). Exp. Neurol. 167, 189–195.

    PubMed  Google Scholar 

  • Bezard, E., Gross, C. E., Fournier, M. C., Dovero, S., Bloch, B., and Jaber, M. (1999). Exp. Neurol. 155, 268–273.

    PubMed  Google Scholar 

  • Chan, P., DeLanney, L. E., Irwin, I., Langston, J. W., and Di, Monte. D. (1991). J. Neurochem. 57, 348–351.

    PubMed  Google Scholar 

  • Chiba, K., Peterson, L. A., Castagnoli, K. P., Trevor, A. J., and Castagnoli, N., Jr. (1985). Drug Metab. Dispos. 13, 342–347.

    PubMed  Google Scholar 

  • Chiba, K., Trevor, A., Castagnoli, N., Jr. (1984). Biochem. Biophys. Res. Commun. P574–P578.

  • Dauer, W., and Przedborski, S. (2003). Neuron 39, 889–909.

    PubMed  Google Scholar 

  • Davey, G. P., and Clark, J. B. (1996). J. Neurochem. 66, 1617–1624.

    PubMed  Google Scholar 

  • Davey, G. P., Tipton, K. F., and Murphy, M. P. (1992). Biochem. J. 288, 439–443.

    PubMed  Google Scholar 

  • Di Monte, D., Jewell, S. A., Ekstrom, G., Sandy, M. S., and Smith, M. T. (1986). Biochem. Biophys. Res. Commun. 137, 310–315.

    PubMed  Google Scholar 

  • Gluck, M. R., Krueger, M. J., Ramsay, R. R., Sablin, S. O., Singer, T. P., and Nicklas, W. J. (1994). J. Biol. Chem. 269, 3167–3174.

    PubMed  Google Scholar 

  • Hasegawa, E., Takeshige, K., Oishi, T., Murai, Y., and Minakami, S. (1990). Biochem. Biophys. Res. Commun. 170, 1049–1055.

    PubMed  Google Scholar 

  • Heikkila, R. E., Manzino, L., Cabbat, F. S., and Duvoisin, R. C. (1984). Nature 311, 467–469.

    PubMed  Google Scholar 

  • Heikkila, R. E., Sieber, B. A., Manzino, L., and Sonsalla, P. K. (1989). Mol. Chem. Neuropathol. 10, 171–183.

    PubMed  Google Scholar 

  • Hoppel, C. L., Grinblatt, D., Kwok, H. C., Arora, P. K., Singh, M. P., Sayre, L. M., and Greenblatt, D. (1987). Biochem. Biophys. Res. Commun. 148, 684–693.

    PubMed  Google Scholar 

  • Jackson-Lewis, V., Jakowec, M., Burke, R. E., and Przedborski, S. (1995). Neurodegeneration 4, 257–269.

    PubMed  Google Scholar 

  • Javitch, J. A., D'Amato, R. J., Strittmatter, S. M., and Snyder, S. H. (1985). Proc. Natl. Acad. Sci. U.S.A. 82, 2173–2177.

    PubMed  Google Scholar 

  • Kitahama, K., Denney, R. M., Maeda, T., and Jouvet, M. (1991). Neuro-science 44, 185–204.

    Google Scholar 

  • Klivenyi, P., St Clair, D., Wermer, M., Yen, H. C., Oberley, T., Yang, L., and Beal, M. F. (1998). Neurobiol. Dis. 5, 253–258.

    PubMed  Google Scholar 

  • Krueger, M. J., Sablin, S. O., Ramsay, R., and Singer, T. P. (1993). J. Neurochem. 61, 1546–1548.

    PubMed  Google Scholar 

  • Langston, J. W., and Irwin, I. (1986). Clin. Neuropharmacol. 9, 485–507.

    Google Scholar 

  • Markey, S. P., Johannessen, J. N., Chiueh, C. C., Bums, R. S., and Herkenham, M. A. (1984). Nature 311, 464–467.

    PubMed  Google Scholar 

  • Miyoshi, H., Inoue, M., Okamoto, S., Ohshima, M., Sakamoto, K., and Iwamura, H. (1997). J. Biol. Chem. 272, 16176–16183.

    PubMed  Google Scholar 

  • Miyoshi, H., Iwata, J., Sakamoto, K., Furukawa, H., Takada, M., Iwamura, H., Watanabe, T., and Kodama, Y. (1998). J. Biol. Chem. 273, 17368–17374.

    PubMed  Google Scholar 

  • Mizuno, Y., Saitoh, T., and Sone, N. (1987a). Biochem. Biophys. Res. Commun. 143, 971–976.

    PubMed  Google Scholar 

  • Mizuno, Y., Sone, N., and Saitoh, T. (1987b). J. Neurochem. 48, 1787–1793.

    PubMed  Google Scholar 

  • Nicklas, W. J., Vyas, I., and Heikkila, R. E. (1985). Life Sci. 36, 2503–2508.

    PubMed  Google Scholar 

  • Peterson, L. A., Caldera, P. S., Trevor, A., Chiba, K., and Castagnoli, N., Jr. (1985). J. Med. Chem. 28, 1432–1436.

    PubMed  Google Scholar 

  • Przedborski, S., and Vila, M. (2003). Ann. N. Y. Acad. Sci. 991, 189–198.

    PubMed  Google Scholar 

  • Ramsay, R. R., Dadgar, J., Trevor, A., and Singer, T. P. (1986). Life Sci. 39, 581–588.

    PubMed  Google Scholar 

  • Ramsay, R. R., Kowal, A. T., Johnson, M. K., Salach, J. I., and Singer, T. P. (1987). Arch. Biochem. Biophys. 259, 645–649.

    PubMed  Google Scholar 

  • Ramsay, R. R., Krueger, M. J., Youngster, S. K., Gluck, M. R., Casida, J. E., and Singer, T. P. (1991a). J. Neurochem. 56, 1184–1190.

    PubMed  Google Scholar 

  • Ramsay, R. R., Krueger, M. J., Youngster, S. K., and Singer, T. P. (1991b). Biochem. J. 273, 481–484.

    PubMed  Google Scholar 

  • Ramsay, R. R., and Singer, T. P. (1986). J. Biol. Chem. 261, 7585–7587.

    PubMed  Google Scholar 

  • Ramsay, R. R., and Singer, T. P. (1992). Biochem. Biophys. Res. Commun. 189, 47–52.

    PubMed  Google Scholar 

  • Ramsay, R. R., Youngster, S. K., Nicklas, W. J., McKeown, K. A., Jin, Y. Z., Heikkila, R. E., and Singer, T. P. (1989). Proc. Natl. Acad. Sci. U.S.A. 86, 9168–9172.

    PubMed  Google Scholar 

  • Riachi, N. J., LaManna, J. C., and Harik, S. I. (1989). J. Pharmacol. Exp. Ther. 249, 744–748.

    PubMed  Google Scholar 

  • Rossetti, Z. L., Sotgiu, A., Sharp, D. E., Hadjiconstantinou, M., and Neff, M. (1988). Biochem. Pharmacol. 37, 4573–4574.

    PubMed  Google Scholar 

  • Rottenberg, H. (1984). J. Membr. Biol. 81, 127–138.

    PubMed  Google Scholar 

  • Schuler, F., and Casida, J. E. (2001). Biochim. Biophys. Acta 1506, 79–87.

    PubMed  Google Scholar 

  • Schuler, F., Yano, T., Di Bernardo, S., Yagi, T., Yankovskaya, V., Singer, T. P., and Casida, J. E. (1999). Proc. Natl. Acad. Sci. U.S.A. 96, 4149–4153.

    PubMed  Google Scholar 

  • Scotcher, K. P., Irwin, I., DeLanney, L. E., Langston, J. W., Di Monte, D. (1990). J. Neurochem. 54, 1295–1301.

    PubMed  Google Scholar 

  • Singer, T. P., Castagnoli, N., Jr., Ramsay, R. R., and Trevor, A. J. (1987). J. Neurochem. 49, 1–8.

    PubMed  Google Scholar 

  • Tieu, K., Perier, C., Caspersen, C., Teismann, P., Wu, D. C., Yan, S. D., Naini, A., Vila, M., Jackson-Lewis, V., Ramasamy, R., and Przedborski, S. (2003). J. Clin. Invest. 112, 892–901.

    PubMed  Google Scholar 

  • Vila, M., Jackson-Lewis, V., Vukosavic, S., Djaldetti, R., Liberatore, G., Offen, D., Korsmeyer, S. J., and Przedborski, S. (2001). Proc. Natl. Acad. Sci. U.S.A. 98, 2837–2842.

    PubMed  Google Scholar 

  • Vyas, I., Heikkila, R. E., and Nicklas, W. J. (1986). J. Neurochem. 46, 1501–1507.

    PubMed  Google Scholar 

  • Ziering, A., Berger, L., Heinemanm, S. D., and Lee, J. (1947). J. Org. Chem. 12, 894–903.

    Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Columbia University, New York, New York 10032

    Serge Przedborski, Kim Tieu, Celine Perier & Miquel Vila

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  1. Serge Przedborski
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  2. Kim Tieu
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  3. Celine Perier
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  4. Miquel Vila
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Przedborski, S., Tieu, K., Perier, C. et al. MPTP as a Mitochondrial Neurotoxic Model of Parkinson's Disease. J Bioenerg Biomembr 36, 375–379 (2004). https://doi.org/10.1023/B:JOBB.0000041771.66775.d5

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