Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic ne urons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's d isease. Here, we show that the proapoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuronal a poptosis. In adult mice, there is an up-regulation of Bax in the SNpc after MPTP administration and a decrease in Bcl-2. These changes parallel MPTP-i nduced dopaminergic neurodegeneration. We also show that mutant mice lackin g Bax are significantly more resistant to MPTP than their wild-type litterm ates. This study demonstrates that Bax plays a critical role in the MPTP ne urotoxic process and suggests that targeting Bax may provide protective ben efit in the treatment of Parkinson's disease.