PMID- 24769307
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20181202
IS  - 1873-1686 (Electronic)
IS  - 0167-0115 (Linking)
VI  - 190-191
DP  - 2014 May
TI  - Exendin-4 promotes the membrane trafficking of the AMPA receptor GluR1 subunit 
      and ADAM10 in the mouse neocortex.
PG  - 1-11
LID - S0167-0115(14)00036-6 [pii]
LID - 10.1016/j.regpep.2014.04.003 [doi]
AB  - Glucagon-like peptide-1 (GLP-1) is a novel treatment modality for type 2 diabetes 
      mellitus. However, GLP-1 has been suggested as a therapeutic target for 
      Alzheimer's disease (AD). In rodent studies, GLP-1 reduces amyloid beta (Abeta) and 
      facilitates synaptic plasticity. Therefore, in the present study, we investigated 
      how GLP-1 facilitates synaptic plasticity and reduces the Abeta in vivo. Exendin-4, 
      a GLP-1 receptor agonist that can cross the blood brain barrier, was 
      subcutaneously administered to adult mice. We then extracted the total and the 
      plasma membrane proteins from the mouse neocortex. Exendin-4 significantly 
      increased the phosphorylation level of cAMP response element-binding protein 
      (CREB). Consistently, the expression level of brain-derived neurotrophic factor 
      (BDNF), a transcriptional target of CREB, was increased. Furthermore, exendin-4 
      increased the membrane protein level of the AMPA receptor GluR1 subunit and 
      postsynaptic density protein-95 (PSD-95), whereas GluR2 was unaffected. These 
      exendin-4-dependent increases in membrane GluR1, total PSD-95 and BDNF were 
      abrogated by pretreatment with temozolomide (TMZ), a DNA-alkylating agent, 
      indicating that these alterations were dependent on exendin-4-induced 
      transcriptional activity. In addition, we found that exendin-4 increased the 
      level of the alpha-C terminal fragment (alpha-CTF) of amyloid precursor protein (APP). 
      Furthermore, protein levels of both mature and immature ADAM10, the alpha-secretase 
      of APP in the plasma membrane, were increased, whereas the total mature and 
      immature ADAM10 levels were unchanged. These exendin-4-dependent increases in 
      alpha-CTF and ADAM10 were not affected by TMZ. These findings suggested that GLP-1 
      facilitates the GluR1 membrane insertion through CREB activation and increases 
      alpha-secretase activity through ADAM10 membrane trafficking. Upregulation of GluR1 
      and ADAM10 at the plasma membrane were also observed in mice with 
      intracerebroventricular administration of Abeta oligomer, indicating that a part of 
      benefit of exendin-4 against AD may depend on the GluR1 and ADAM10 membrane 
      trafficking.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Ohtake, Nobuaki
AU  - Ohtake N
AD  - Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 
      31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
FAU - Saito, Mieko
AU  - Saito M
AD  - Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 
      31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
FAU - Eto, Masaaki
AU  - Eto M
AD  - Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 
      31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
FAU - Seki, Kenjiro
AU  - Seki K
AD  - Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 
      31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan. Electronic 
      address: k-seki@pha.ohu-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140424
PL  - Netherlands
TA  - Regul Pept
JT  - Regulatory peptides
JID - 8100479
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptides)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Venoms)
RN  - 9P1872D4OL (Exenatide)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.81 (ADAM10 Protein)
RN  - EC 3.4.24.81 (Adam10 protein, mouse)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
SB  - IM
CIN - Regul Pept. 2014 Jun-Aug;192-193:55-6. PMID: 24882709
MH  - ADAM Proteins/*metabolism
MH  - ADAM10 Protein
MH  - Amyloid Precursor Protein Secretases/*metabolism
MH  - Animals
MH  - Cell Membrane/*drug effects/*metabolism
MH  - Exenatide
MH  - Infusions, Intraventricular
MH  - Male
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Neocortex/*cytology/*drug effects
MH  - Peptides/administration & dosage/*pharmacology
MH  - Receptors, AMPA/*metabolism
MH  - Venoms/administration & dosage/*pharmacology
OTO - NOTNLM
OT  - ADAM10
OT  - AMPA receptor GluR1 subunit
OT  - Exendin-4
OT  - Glucagon-like peptide-1
OT  - Mouse neocortex
EDAT- 2014/04/29 06:00
MHDA- 2015/03/31 06:00
CRDT- 2014/04/29 06:00
PHST- 2013/12/20 00:00 [received]
PHST- 2014/04/06 00:00 [revised]
PHST- 2014/04/12 00:00 [accepted]
PHST- 2014/04/29 06:00 [entrez]
PHST- 2014/04/29 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
AID - S0167-0115(14)00036-6 [pii]
AID - 10.1016/j.regpep.2014.04.003 [doi]
PST - ppublish
SO  - Regul Pept. 2014 May;190-191:1-11. doi: 10.1016/j.regpep.2014.04.003. Epub 2014 
      Apr 24.