期刊
JOURNAL OF NEUROCHEMISTRY
卷 98, 期 4, 页码 1068-1077出版社
WILEY
DOI: 10.1111/j.1471-4159.2006.03931.x
关键词
dephosphorylation; mammalian target of rapamycin; ribosomal protein kinase; phosphoinositide-dependent protein kinase 1; tau; troglitazone
资金
- PHS HHS [38623] Funding Source: Medline
Peroxisome proliferator-activated receptor-gamma (PPAR gamma), a member of the nuclear receptor superfamily, is activated by several compounds including the thiazolidinediones. In addition to being a target for diabetes, PPAR gamma activation state has recently been shown to modulate beta-amyloid peptide (A beta) production in cellular models relevant to Alzheimer's disease. Here, we report the effect of troglitazone, a thiazolidinedione, in cells expressing 4-repeat tau. A 24 h treatment with troglitazone significantly reduced phosphorylation of tau at Ser202 and Ser396/404, residues of early and later stages of neurofibrillary tangle accumulation in Alzheimer's disease and other neurodegenerative disorders. Under the same experimental conditions the level of tau did not change. In our cellular model, troglitazone appeared to enhance 3'-phosphoinositide-dependent protein kinase 1 (PDK1) nuclear translocation, resulting in a decrease in cytosolic phosphorylated 70 kDa ribosomal protein kinase (p70S6) and phosphorylated mammalian target of rapamycin (mTor). Furthermore, PPAR gamma transcriptional activity did not appear to be responsible for decreased phosphorylation of tau. Thus, we believe that the thiazolidinedione regulates tau phosphorylation through a PPAR gamma-dependent/independent mechanism involving an Akt/glycogen synthase kinase-3(GSK-3 beta)-independent signalling cascade: PDK1/p70S6K/mTor.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据