PMID- 16787414
OWN - NLM
STAT- MEDLINE
DCOM- 20060921
LR  - 20211203
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 98
IP  - 4
DP  - 2006 Aug
TI  - Troglitazone, a peroxisome proliferator-activated receptor-gamma agonist, 
      decreases tau phosphorylation in CHOtau4R cells.
PG  - 1068-77
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the 
      nuclear receptor superfamily, is activated by several compounds including the 
      thiazolidinediones. In addition to being a target for diabetes, PPARgamma 
      activation state has recently been shown to modulate beta-amyloid peptide (Abeta) 
      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, PPARgamma transcriptional activity did not appear to be responsible 
      for decreased phosphorylation of tau. Thus, we believe that the thiazolidinedione 
      regulates tau phosphorylation through a PPARgamma-dependent/independent mechanism 
      involving an Akt/glycogen synthase kinase-3(GSK-3beta)-independent signalling 
      cascade: PDK1/p70S6K/mTor.
FAU - d'Abramo, Cristina
AU  - d'Abramo C
AD  - Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 
      10461, USA.
FAU - Ricciarelli, Roberta
AU  - Ricciarelli R
FAU - Pronzato, Maria A
AU  - Pronzato MA
FAU - Davies, Peter
AU  - Davies P
LA  - eng
GR  - 38623/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060619
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Chromans)
RN  - 0 (PPAR gamma)
RN  - 0 (Thiazolidinediones)
RN  - 0 (tau Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Animals
MH  - Blotting, Western
MH  - CHO Cells
MH  - Cell Nucleus/drug effects/metabolism
MH  - Chromans/*pharmacology
MH  - Cricetinae
MH  - Cytosol/drug effects/metabolism
MH  - Depression, Chemical
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Neurofibrillary Tangles/metabolism
MH  - PPAR gamma/*agonists
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases
MH  - Thiazolidinediones/*pharmacology
MH  - Transfection
MH  - Troglitazone
MH  - tau Proteins/*metabolism
EDAT- 2006/06/22 09:00
MHDA- 2006/09/22 09:00
CRDT- 2006/06/22 09:00
PHST- 2006/06/22 09:00 [pubmed]
PHST- 2006/09/22 09:00 [medline]
PHST- 2006/06/22 09:00 [entrez]
AID - JNC3931 [pii]
AID - 10.1111/j.1471-4159.2006.03931.x [doi]
PST - ppublish
SO  - J Neurochem. 2006 Aug;98(4):1068-77. doi: 10.1111/j.1471-4159.2006.03931.x. Epub 
      2006 Jun 19.