Abstract:
:Increased protein aggregation and altered cell signaling accompany many neurodegenerative diseases including Huntington's disease (HD). Cell stress is counterbalanced by signals mediating cell repair but the identity of these are not fully understood. We show here that the mammalian target of rapamycin (mTOR) pathway is inhibited and cytoprotective autophagy is activated in neuronal PC6.3 cells at 24 h after expression of mutant huntingtin proteins. Tuberous sclerosis complex (TSC) 1/2 interacted with growth arrest and DNA damage protein 34 (GADD34), which caused TSC2 dephosphorylation and induction of autophagy in mutant huntingtin expressing cells. However, GADD34 and autophagy decreased at later time points, after 48 h of transfection with the concomitant increase in mTOR activity. Overexpression of GADD34 counteracted these effects and increased cytoprotective autophagy and cell survival. These results show that GADD34 plays an important role in cell protection in mutant huntingtin expressing cells. Modulation of GADD34 and the TSC pathway may prove useful in counteracting cell degeneration accompanying HD and other neurodegenerative diseases.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Hyrskyluoto A,Reijonen S,Kivinen J,Lindholm D,Korhonen Ldoi
10.1016/j.yexcr.2011.08.020subject
Has Abstractpub_date
2012-01-01 00:00:00pages
33-42issue
1eissn
0014-4827issn
1090-2422pii
S0014-4827(11)00343-0journal_volume
318pub_type
杂志文章abstract::Acetylcholine receptors (AChRs) of rat muscle cells grown in culture for 4 days were labeled with 125I-alpha-bungarotoxin and their degradation rate measured. Two AChR populations, a rapidly degrading one (Rr,t1/2 approximately 1 day) and a slowly degrading one (Rs, t1/2 approximately 4 days) were identified at a rati...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1993.1220
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journal_title:Experimental cell research
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
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doi:10.1016/j.yexcr.2004.03.021
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journal_title:Experimental cell research
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2008.11.021
更新日期:2009-04-15 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(85)90230-7
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journal_title:Experimental cell research
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
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journal_title:Experimental cell research
pub_type: 杂志文章
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