PMID- 24094580
OWN - NLM
STAT- MEDLINE
DCOM- 20140929
LR  - 20240423
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Print)
IS  - 0197-4580 (Linking)
VI  - 35
IP  - 3
DP  - 2014 Mar
TI  - beta-amyloid impairs the regulation of N-methyl-D-aspartate receptors by glycogen 
      synthase kinase 3.
PG  - 449-59
LID - S0197-4580(13)00382-5 [pii]
LID - 10.1016/j.neurobiolaging.2013.08.031 [doi]
AB  - Accumulating evidence suggests that glycogen synthase kinase 3 (GSK-3) is a 
      multifunctional kinase implicated in Alzheimer's disease (AD). However, the 
      synaptic actions of GSK-3 in AD conditions are largely unknown. In this study, we 
      examined the impact of GSK-3 on N-methyl-D-aspartate receptor (NMDAR) channels, 
      the major mediator of synaptic plasticity. Application of GSK-3 inhibitors or 
      knockdown of GSK-3 caused a significant reduction of NMDAR-mediated ionic and 
      synaptic current in cortical neurons, whereas this effect of GSK-3 was impaired 
      in cortical neurons treated with beta-amyloid (Abeta) or from transgenic mice 
      overexpressing mutant amyloid precursor protein. GSK-3 activity was elevated by 
      Abeta, and GSK-3 inhibitors failed to decrease the surface expression of NMDA 
      receptor NR1 (NR1) and NR1/postsynaptic density-95 (PSD-95) interaction in 
      amyloid precursor protein mice, which was associated with the diminished GSK-3 
      regulation of Rab5 activity that mediates NMDAR internalization. Consequently, 
      GSK-3 inhibitor lost the capability of protecting neurons against 
      N-methyl-D-aspartate-induced excitotoxicity in Abeta-treated neurons. These results 
      have provided a novel mechanism underlying the involvement of GSK-3 in AD.
CI  - Published by Elsevier Inc.
FAU - Deng, Yulei
AU  - Deng Y
AD  - Department of Neurology and Institute of Neurology, Ruijin Hospital, School of 
      medicine, Shanghai Jiao Tong University, Shanghai, China; Department of 
      Physiology and Biophysics, State University of New York at Buffalo, School of 
      Medicine and Biomedical Sciences, Buffalo, NY, USA.
FAU - Xiong, Zhe
AU  - Xiong Z
FAU - Chen, Paul
AU  - Chen P
FAU - Wei, Jing
AU  - Wei J
FAU - Chen, Shengdi
AU  - Chen S
FAU - Yan, Zhen
AU  - Yan Z
LA  - eng
GR  - R01 MH085774/MH/NIMH NIH HHS/United States
GR  - MH085774/MH/NIMH NIH HHS/United States
GR  - I01 BX001633/BX/BLRD VA/United States
GR  - R01 MH084233/MH/NIMH NIH HHS/United States
GR  - MH084233/MH/NIMH NIH HHS/United States
GR  - R21 MH101690/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20131001
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Indoles)
RN  - 0 (Maleimides)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (SB 216763)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.6.5.2 (rab5 GTP-Binding Proteins)
SB  - IM
MH  - Alzheimer Disease/*drug therapy/*genetics
MH  - Amyloid beta-Peptides/*physiology
MH  - Animals
MH  - Apoptosis
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Disease Models, Animal
MH  - Glycogen Synthase Kinase 3/*antagonists & inhibitors/*physiology
MH  - Indoles/pharmacology/therapeutic use
MH  - Male
MH  - Maleimides/pharmacology/therapeutic use
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Targeted Therapy
MH  - N-Methylaspartate/toxicity
MH  - Neuronal Plasticity/drug effects/genetics
MH  - Neurons/*metabolism/*pathology
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism/*physiology
MH  - rab5 GTP-Binding Proteins/metabolism/physiology
PMC - PMC7034321
MID - NIHMS712306
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - GSK-3
OT  - NMDA receptor
OT  - beta-amyloid
COIS- Conflict of interest None of the authors have actual or potential conflicts of 
      interest. None of the authors' institution has contracts relating to this 
      research. There is no other agreement of authors or their institutions that could 
      be seen as involving a financial interest in this work.
EDAT- 2013/10/08 06:00
MHDA- 2014/09/30 06:00
PMCR- 2020/02/21
CRDT- 2013/10/08 06:00
PHST- 2013/03/19 00:00 [received]
PHST- 2013/08/27 00:00 [revised]
PHST- 2013/08/29 00:00 [accepted]
PHST- 2013/10/08 06:00 [entrez]
PHST- 2013/10/08 06:00 [pubmed]
PHST- 2014/09/30 06:00 [medline]
PHST- 2020/02/21 00:00 [pmc-release]
AID - S0197-4580(13)00382-5 [pii]
AID - 10.1016/j.neurobiolaging.2013.08.031 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2014 Mar;35(3):449-59. doi: 
      10.1016/j.neurobiolaging.2013.08.031. Epub 2013 Oct 1.