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Necrosis inhibitor-5 (NecroX-5), attenuates MPTP-induced motor deficits in a zebrafish model of Parkinson’s disease

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Abstract

In the present study, necrosis inhibitor-5 (NecroX-5), a novel Cyclopentylamino carboxymethylthiazolylindole (NecroX) series compound was investigated for its protective role against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a zebrafish model of Parkinson’s disease (PD). MPTP-induced locomotor behavior was measured in zebrafish larvae and the protein expression level of tyrosine hydroxylase (TH) was estimated in zebrafish larva homogenates. MPTP (15 μM) induced a significant (p < 0.05) impairment in zebrafish larvae locomotor behavior. Treatment with NecroX-5 at various doses (3.75, 7.5 and 15 μM) significantly and dose dependently (p < 0.05) restored MPTP-induced locomotor impairments in zebrafish larvae. Further, NecroX-5 significantly attenuated the MPTP-induced decrease in zebrafish TH protein expression levels. The effects observed by NecroX-5 were almost two fold higher when compared with the antioxidant, minocycline. In conclusion, the neuroprotective activity exhibited by NecroX-5 by attenuating MPTP-induced locomotor impairments and dopaminergic TH expression in zebrafish warrants further development of NecroX-5 as a novel neuroprotectant in the treatment of neurodegenerative disorders including PD.

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Acknowledgments

The National Research Foundation of Korea (NRF-2010-0012391) supported this work.

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    Authors and Affiliations

    1. Department of Biotechnology, Konkuk University, Chungju, 27478, South Korea

      Jun-Cheng Liu, Sushruta Koppula, Se-Jong Huh, Pyo-Jam Park & Chan-Gil Kim

    2. Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, South Korea

      Chul-Geun Kim

    3. Department of Biological Sciences, Institute of Molecular and Cellular Biology, Inha University, Incheon, 402-751, South Korea

      Chang-Joong Lee

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    1. Jun-Cheng Liu
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    2. Sushruta Koppula
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    Correspondence to Chan-Gil Kim.

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    All authors have declared no conflict of interest.

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    Jun-Cheng Liu and Sushruta Koppula contributed equally to this work.

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    Liu, JC., Koppula, S., Huh, SJ. et al. Necrosis inhibitor-5 (NecroX-5), attenuates MPTP-induced motor deficits in a zebrafish model of Parkinson’s disease. Genes Genom 37, 1073–1079 (2015). https://doi.org/10.1007/s13258-015-0364-4

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    • DOI: https://doi.org/10.1007/s13258-015-0364-4

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