Abstract：
:Early onset familial Alzheimer's disease (FAD) is linked to autosomal dominant mutations in the amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2) genes. These are critical mediators of total amyloid beta-peptide (Abeta) production, inducing cell death through uncertain mechanisms. Tauroursodeoxycholic acid (TUDCA) modulates exogenous Abeta-induced apoptosis by interfering with E2F-1/p53/Bax. Here, we used mouse neuroblastoma cells that express either wild-type APP, APP with the Swedish mutation (APPswe), or double-mutated human APP and PS1 (APPswe/DeltaE9), all exhibiting increased Abeta production and aggregation. Cell viability was decreased in APPswe and APPswe/DeltaE9 but was partially reversed by z-VAD.fmk. Nuclear fragmentation and caspase 2, 6 and 8 activation were also readily detected. TUDCA reduced nuclear fragmentation as well as caspase 2 and 6, but not caspase 8 activities. p53 activity, and Bcl-2 and Bax changes, were also modulated by TUDCA. Overexpression of p53, but not mutant p53, in wild-type and mutant neuroblastoma cells was sufficient to induce apoptosis, which, in turn, was reduced by TUDCA. In addition, inhibition of the phosphatidylinositide 3'-OH kinase pathway reduced TUDCA protection against p53-induced apoptosis. In conclusion, FAD mutations are associated with the activation of classical apoptotic pathways. TUDCA reduces p53-induced apoptosis and modulates expression of Bcl-2 family.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Ramalho RM,Borralho PM,Castro RE,Solá S,Steer CJ,Rodrigues CMdoi
10.1111/j.1471-4159.2006.04007.xsubject
Has Abstractpub_date
2006-09-01 00:00:00pages
1610-8issue
5eissn
0022-3042issn
1471-4159pii
JNC4007journal_volume
98pub_type
杂志文章abstract：:Although palmitoylation of the beta(2)-adrenergic receptor (beta(2)AR), as well as its phosphorylation by the cyclic AMP-dependant protein kinase (PKA) and the beta-adrenergic receptor kinase (beta ARK), are known to play important roles in agonist-promoted desensitization, their relative contribution and mutual regul...
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更新日期：2004-05-01 00:00:00
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journal_title：Journal of neurochemistry
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更新日期：1993-11-01 00:00:00
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更新日期：2002-12-01 00:00:00
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更新日期：2002-09-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：1994-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：2006-10-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
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更新日期：2016-12-01 00:00:00
