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 neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the proapoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuro...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2001-02, Vol.98 (5), p.2837-2842 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Vila, Miquel Jackson-Lewis, Vernice Vukosavic, Slobodanka Djaldetti, Ruth Liberatore, Gabriel Offen, Daniel Korsmeyer, Stanley J. Przedborski, Serge |
| description | 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 proapoptotic 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. |
| doi_str_mv | 10.1073/pnas.051633998 |
| format | Article |
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Here, we show that the proapoptotic 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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.051633998</identifier><identifier>PMID: 11226327</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology ; Animals ; Apoptosis ; Base Sequence ; bcl-2-Associated X Protein ; Biological Sciences ; Cell death ; Dimerization ; Disease Models, Animal ; DNA Primers ; Dopamine - metabolism ; Dopaminergic neurons ; Immunoprecipitation ; Mesencephalon - metabolism ; Messenger RNA ; Mice ; Mice, Inbred C57BL ; Midbrain ; Neurology ; Neurons ; Parkinson disease ; Parkinson Disease - genetics ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Parkinson's disease ; Proteins ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins c-bcl-2 ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Up regulation</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2001-02, Vol.98 (5), p.2837-2842</ispartof><rights>Copyright 1993-2001 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 27, 2001</rights><rights>Copyright © 2001, The National Academy of Sciences 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c582t-ae626bdc9fd4a9b350904d45af3f14890c8a443be143fe4c0aa634a55279c2553</citedby><cites>FETCH-LOGICAL-c582t-ae626bdc9fd4a9b350904d45af3f14890c8a443be143fe4c0aa634a55279c2553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/98/5.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3055144$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3055144$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11226327$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vila, Miquel</creatorcontrib><creatorcontrib>Jackson-Lewis, Vernice</creatorcontrib><creatorcontrib>Vukosavic, Slobodanka</creatorcontrib><creatorcontrib>Djaldetti, Ruth</creatorcontrib><creatorcontrib>Liberatore, Gabriel</creatorcontrib><creatorcontrib>Offen, Daniel</creatorcontrib><creatorcontrib>Korsmeyer, Stanley J.</creatorcontrib><creatorcontrib>Przedborski, Serge</creatorcontrib><title>Bax Ablation Prevents Dopaminergic Neurodegeneration in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson's Disease</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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. 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Here, we show that the proapoptotic 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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>11226327</pmid><doi>10.1073/pnas.051633998</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology Animals Apoptosis Base Sequence bcl-2-Associated X Protein Biological Sciences Cell death Dimerization Disease Models, Animal DNA Primers Dopamine - metabolism Dopaminergic neurons Immunoprecipitation Mesencephalon - metabolism Messenger RNA Mice Mice, Inbred C57BL Midbrain Neurology Neurons Parkinson disease Parkinson Disease - genetics Parkinson Disease - metabolism Parkinson Disease - pathology Parkinson's disease Proteins Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins c-bcl-2 RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Up regulation |
| title | Bax Ablation Prevents Dopaminergic Neurodegeneration in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson's Disease |
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