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PMID: 11226327 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 5 ·2001-02-27 ·Pages 2837-42

Vila M, Jackson-Lewis V, Vukosavic S, Djaldetti R, Liberatore G, Offen D, Korsmeyer SJ, Przedborski S

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.

MeSH Terms
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology Animals Base Sequence DNA Primers Dimerization Disease Models, Animal Dopamine/metabolism Mesencephalon/metabolism Mice Mice, Inbred C57BL Parkinson Disease/genetics,metabolism,pathology Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-bcl-2 RNA, Messenger/genetics,metabolism Up-Regulation bcl-2-Associated X Protein
Chemicals
Bax protein, mouse DNA Primers Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 RNA, Messenger bcl-2-Associated X Protein 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Dopamine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Vila M
Department of Neurology, Columbia University, 650 West 168th Street, New York, NY 10032, USA.
Jackson-Lewis V
Vukosavic S
Djaldetti R
Liberatore G
Offen D
Korsmeyer S J
Przedborski S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.051633998
Published
2001-02-27
Epub
2001-00-13
Pages
2837-42
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC30226
Subset
IM
Grants
NINDS NIH HHS · R01 NS38586 · United States
NINDS NIH HHS · P50 NS038370 · United States
NINDS NIH HHS · P50 NS38370 · United States
NINDS NIH HHS · R29 NS37345 · United States
NINDS NIH HHS · R01 NS038586 · United States
External Links
PubMed source DOI: 10.1073/pnas.051633998 PMC Full Text View journal details
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