PMID- 20699650
OWN - NLM
STAT- MEDLINE
DCOM- 20110512
LR  - 20211020
IS  - 1933-6969 (Electronic)
IS  - 1933-6950 (Print)
IS  - 1933-6950 (Linking)
VI  - 4
IP  - 5
DP  - 2010 Sep-Oct
TI  - The role of STEP in Alzheimer's disease.
PG  - 347-50
LID - 10.1523/JNEUROSCI.0157-10.2010 [doi]
AB  - Amyloid beta (Abeta), the putative causative agent in Alzheimer's disease, is known 
      to affect glutamate receptor trafficking. Previous studies have shown that Abeta 
      downregulates the surface expression of N-methyl D-aspartate type glutamate 
      receptors (NMDARs) by the activation of STriatal-Enriched protein tyrosine 
      Phosphatase 61 (STEP(6)(1)). More recent findings confirm that STEP(6)(1) plays an 
      important role in Abeta-induced NMDAR endocytosis. STEP levels are elevated in human 
      AD prefrontal cortex and in the cortex of several AD mouse models. The increase 
      in STEP(6)(1) levels and activity contribute to the removal of GluN1/GluN2B receptor 
      complexes from the neuronal surface membranes. The elevation of STEP(6)(1) is due to 
      disruption in the normal degradation of STEP(6)(1) by the ubiquitin proteasome 
      system. Here, we briefly discuss additional studies in support of our hypothesis 
      that STEP(6)(1) contributes to aspects of the pathophysiology in Alzheimer's disease. 
      Exogenous application of Abeta-enriched conditioned medium (7PA2-CM) to wild-type 
      cortical cultures results in a loss of GluN1/GluN2B subunits from neuronal 
      membranes. Abeta-mediated NMDAR internalization does not occur in STEP knock-out 
      cultures, but is rescued by the addition of active TAT-STEP to the cultures prior 
      to Abeta treatment.
FAU - Kurup, Pradeep
AU  - Kurup P
AD  - Child Study Center, Yale University School of Medicine, New Haven, CT, USA.
FAU - Zhang, Yongfang
AU  - Zhang Y
FAU - Venkitaramani, Deepa V
AU  - Venkitaramani DV
FAU - Xu, Jian
AU  - Xu J
FAU - Lombroso, Paul J
AU  - Lombroso PJ
LA  - eng
GR  - K02 MH001527/MH/NIMH NIH HHS/United States
GR  - R01 MH052711/MH/NIMH NIH HHS/United States
GR  - MH52711/MH/NIMH NIH HHS/United States
GR  - MH01527/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100906
PL  - United States
TA  - Channels (Austin)
JT  - Channels (Austin, Tex.)
JID - 101321614
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 3.1.3.48 (PTPN5 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor)
SB  - IM
CON - Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, et al. 
      Abeta-mediated NMDA receptor endocytosis in Alzheimer's disease involves 
      ubiquitination of the tyrosine phosphatase STEP61. J Neurosci. 2010;30:5948-5957. 
      doi: 10.1523/JNEUROSCI.0157-10.2010. PMID: 20427654
MH  - Alzheimer Disease/*etiology/physiopathology
MH  - Amyloid beta-Peptides
MH  - Amyloid beta-Protein Precursor
MH  - Animals
MH  - Cells, Cultured
MH  - Humans
MH  - Mice
MH  - Prefrontal Cortex
MH  - Protein Transport
MH  - Protein Tyrosine Phosphatases, Non-Receptor/*physiology
MH  - Receptors, Glutamate/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
PMC - PMC3230511
EDAT- 2010/08/12 06:00
MHDA- 2011/05/13 06:00
PMCR- 2010/09/01
CRDT- 2010/08/12 06:00
PHST- 2010/08/12 06:00 [entrez]
PHST- 2010/08/12 06:00 [pubmed]
PHST- 2011/05/13 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - 12910 [pii]
AID - 1933-6950-4-5-3 [pii]
AID - 10.1523/JNEUROSCI.0157-10.2010 [doi]
PST - ppublish
SO  - Channels (Austin). 2010 Sep-Oct;4(5):347-50. doi: 10.1523/JNEUROSCI.0157-10.2010. 
      Epub 2010 Sep 6.