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Proteasome Inhibitor Does Not Enhance MPTP Neurotoxicity in Mice

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Abstract

Dysfunction of the proteasome function is known to be a potential mechanism for dopaminergic neuron degeneration. Here, we investigated to determine whether systematic administration of proteasome inhibitor, carbobenzoxy-l-γ-t-butyl-l-glutamyl-l-alanyl-l-leucinal (PSI), causes the increased susceptibility in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. PSI was injected into MPTP-treated mice over a period of 2 weeks. Thereafter, we evaluated the effect of PSI 2, 4, and 8 weeks after the cessation of treatment with PSI. In the present study with HPLC analysis, PSI did not enhance MPTP-induced dopaminergic neurotoxicity in mice. Our present study with Western blot analysis also demonstrated that the reduction of tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) protein levels in MPTP-treated mice was more pronounced than that in MPTP + PSI-treated animals. These results suggest that proteasome inhibitor did not enhance MPTP neurotoxicity in mice. Our findings suggest that proteasome inhibition is not a reliable model for PD. Thus, our findings provide further valuable information for the pathogenesis of Parkinson’s disease.

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Acknowledgments

This study was supported in part by Grant-in-Aid for Scientific Research (136700627 and 13671095) from the Ministry of Science and Education in Japan.

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Authors and Affiliations

  1. Department of Neurobiology and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78, Sho-machi, Tokushima, 770-8505, Japan

    Naoto Kadoguchi, Masahiro Umeda & Tsutomu Araki

  2. Department of Neurology, Organized Center of Clinical Medicine, International University of Health and Welfare, Tochigi, Japan

    Hiroyuki Kato

Authors
  1. Naoto Kadoguchi
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  2. Masahiro Umeda
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  3. Hiroyuki Kato
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  4. Tsutomu Araki
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Corresponding author

Correspondence to Tsutomu Araki.

Additional information

Naoto Kadoguchi and Masahiro Umeda contributed equally to this work.

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Kadoguchi, N., Umeda, M., Kato, H. et al. Proteasome Inhibitor Does Not Enhance MPTP Neurotoxicity in Mice. Cell Mol Neurobiol 28, 971–979 (2008). https://doi.org/10.1007/s10571-008-9271-4

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  • DOI: https://doi.org/10.1007/s10571-008-9271-4

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