14-3-3theta protects against neurotoxicity in a cellular Parkinson's disease model through inhibition of the apoptotic factor Bax.
14-3-3theta protects against neurotoxicity in a cellular Parkinson's disease model through inhibition of the apoptotic factor Bax.
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DOI：
10.1371/journal.pone.0021720
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Yacoubian TA
中科院分区：
文献类型：
--
作者：
Slone SR;Lesort M;Yacoubian TA
Disruption of 14-3-3 function by alpha-synuclein has been implicated in Parkinson's disease. As 14-3-3s are important regulators of cell death pathways, disruption of 14-3-3s could result in the release of pro-apoptotic factors, such as Bax. We have previously shown that overexpression of 14-3-3θ reduces cell loss in response to rotenone and MPP+ in dopaminergic cell culture and reduces cell loss in transgenic C. elegans that overexpress alpha-synuclein. In this study, we investigate the mechanism for 14-3-3θ's neuroprotection against rotenone toxicity. While 14-3-3s can inhibit many pro-apoptotic factors, we demonstrate that inhibition of one factor in particular, Bax, is important to 14-3-3s' protection against rotenone toxicity in dopaminergic cells. We found that 14-3-3θ overexpression reduced Bax activation and downstream signaling events, including cytochrome C release and caspase 3 activation. Pharmacological inhibition or shRNA knockdown of Bax provided protection against rotenone, comparable to 14-3-3θ's neuroprotective effects. A 14-3-3θ mutant incapable of binding Bax failed to protect against rotenone. These data suggest that 14-3-3θ's neuroprotective effects against rotenone are at least partially mediated by Bax inhibition and point to a potential therapeutic role of 14-3-3s in Parkinson's disease.
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影响因子：
25
作者：
Nagai, Makiko;Re, Diane B.;Przedborski, Serge
通讯作者：
Przedborski, Serge
影响因子：
--
作者：
Firestone, JA;Smith-Weller, T;Checkoway, H
通讯作者：
Checkoway, H
DOI：
10.1073/pnas.0508215102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Perier, C;Tieu, K;Vila, M
通讯作者：
Vila, M
影响因子：
3.5
作者：
Choo, YS;Johnson, GVW;Lesort, M
通讯作者：
Lesort, M
影响因子：
4.8
作者：
Qi, XJ;Wildey, GM;Howe, PH
通讯作者：
Howe, PH