Abstract
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the pro-apoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuronal apoptosis. 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-induced dopaminergic neurodegeneration. We also show that mutant mice lacking Bax are significantly more resistant to MPTP than their wild-type littermates. This study demonstrates that Bax plays a critical role in the MPTP neurotoxic process and suggests that targeting Bax may provide protective benefit in the treatment of Parkinson's disease.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
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Animals
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Base Sequence
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DNA Primers
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Dimerization
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Disease Models, Animal
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Dopamine / metabolism*
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Mesencephalon / metabolism
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Mice
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Mice, Inbred C57BL
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Parkinson Disease / genetics
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Parkinson Disease / metabolism
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Parkinson Disease / pathology*
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins c-bcl-2*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Up-Regulation
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bcl-2-Associated X Protein
Substances
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Bax protein, mouse
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DNA Primers
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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bcl-2-Associated X Protein
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Dopamine