PMID- 15184080
OWN - NLM
STAT- MEDLINE
DCOM- 20040730
LR  - 20181130
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 319
IP  - 3
DP  - 2004 Jul 2
TI  - The retinoic acid and brain-derived neurotrophic factor differentiated SH-SY5Y 
      cell line as a model for Alzheimer's disease-like tau phosphorylation.
PG  - 993-1000
AB  - The paired helical filaments of highly phosphorylated tau protein are the main 
      components of neurofibrillary tangles (NFT) in Alzheimer's disease (AD). Protein 
      kinases including glycogen synthase kinase 3 beta (GSK3beta), cyclin-dependent 
      kinase 5 (Cdk5), and c-Jun N-terminal kinase (JNK) have been implicated in NFT 
      formation making the use of selective kinase inhibitors an attractive treatment 
      possibility in AD. When sequentially treated with retinoic acid (RA) and 
      brain-derived neurotrophic factor (BDNF), the human neuroblastoma SH-SY5Y 
      differentiates to neuron-like cells. We found that coincident with 
      morphologically evident neurite outgrowth, both the content and phosphorylation 
      state of tau increased in RA-BDNF differentiated SH-SY5Y cells. Tau 
      phosphorylation increased at all the examined sites ser-199, ser-202, thr-205, 
      ser-396, and ser-404, all of which are hyperphosphorylated in AD brain. We also 
      investigated whether GSK3beta, Cdk5 or JNK was involved in tau phosphorylation in 
      the differentiated SH-SY5Y cells. We found that GSK3beta contributed most and 
      that Cdk5 made a minor contribution. JNK was not involved in tau phosphorylation 
      in this system. The GSK3beta-inhibitor, lithium, inhibited tau phosphorylation in 
      a concentration-dependent manner and with good reproducibility, which enables 
      ranking of substances in this cell model. RA-BDNF differentiated SH-SY5Y cells 
      could serve as a suitable model for studying the mechanisms of tau 
      phosphorylation and for screening potential GSK3beta inhibitors.
FAU - Jamsa, Anne
AU  - Jamsa A
AD  - Karolinska Institutet, Neurotec Department, Division of Experimental Geriatrics, 
      Novum, S-141 86, Huddinge, Sweden.
FAU - Hasslund, Kristina
AU  - Hasslund K
FAU - Cowburn, Richard F
AU  - Cowburn RF
FAU - Backstrom, Anders
AU  - Backstrom A
FAU - Vasange, Mervi
AU  - Vasange M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Purines)
RN  - 0 (tau Proteins)
RN  - 0ES1C2KQ94 (Roscovitine)
RN  - 452VLY9402 (Serine)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.22 (CDK5 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Differentiation/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Size
MH  - Cyclin-Dependent Kinase 5
MH  - Cyclin-Dependent Kinases/metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Growth Inhibitors/pharmacology
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neurofibrillary Tangles/chemistry/*metabolism
MH  - Phosphorylation
MH  - Purines/pharmacology
MH  - Roscovitine
MH  - Serine/metabolism
MH  - Tretinoin/*pharmacology
MH  - tau Proteins/*metabolism
EDAT- 2004/06/09 05:00
MHDA- 2004/07/31 05:00
CRDT- 2004/06/09 05:00
PHST- 2004/05/06 00:00 [received]
PHST- 2004/06/09 05:00 [pubmed]
PHST- 2004/07/31 05:00 [medline]
PHST- 2004/06/09 05:00 [entrez]
AID - S0006291X04010253 [pii]
AID - 10.1016/j.bbrc.2004.05.075 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2004 Jul 2;319(3):993-1000. doi: 
      10.1016/j.bbrc.2004.05.075.