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

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 mu M) 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 mu M) 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.