PMID- 27776993
OWN - NLM
STAT- MEDLINE
DCOM- 20171106
LR  - 20171202
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 318
DP  - 2017 Feb 1
TI  - Lixisenatide attenuates the detrimental effects of amyloid beta protein on spatial 
      working memory and hippocampal neurons in rats.
PG  - 28-35
LID - S0166-4328(16)30892-0 [pii]
LID - 10.1016/j.bbr.2016.10.033 [doi]
AB  - Type 2 diabetes mellitus(T2DM) is a risk factor of Alzheimer's disease (AD), 
      which is most likely linked to impairments of insulin signaling in the brain. 
      Hence, drugs enhancing insulin signaling may have therapeutic potential for AD. 
      Lixisenatide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analogue, 
      facilitates insulin signaling and has neuroprotective properties. We previously 
      reported the protective effects of lixisenatide on memory formation and synaptic 
      plasticity. Here, we describe additional key neuroprotective properties of 
      lixisenatide and its possible molecular and cellular mechanisms against 
      AD-related impairments in rats. The results show that lixisenatide effectively 
      alleviated amyloid beta protein (Abeta) 25-35-induced working memory impairment, 
      reversed Abeta25-35-triggered cytotoxicity on hippocampal cell cultures, and 
      prevented against Abeta25-35-induced suppression of the Akt-MEK1/2 signaling 
      pathway. Lixisenatide also reduced the Abeta25-35 acute application induced 
      intracellular calcium overload, which was abolished by U0126, a specific MEK1/2 
      inhibitor. These results further confirmed the neuroprotective and cytoprotective 
      action of lixisenatide against Abeta-induced impairments, suggesting that the 
      protective effects of lixisenatide may involve the activation of the Akt-MEK1/2 
      signaling pathway and the regulation of intracellular calcium homeostasis.
CI  - Crown Copyright A(c) 2016. Published by Elsevier B.V. All rights reserved.
FAU - Cai, Hong-Yan
AU  - Cai HY
AD  - Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 
      030001, China.
FAU - Wang, Zhao-Jun
AU  - Wang ZJ
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Holscher, Christian
AU  - Holscher C
AD  - Division of Biomed and Life Sciences, Faculty of Health and Medicine Lancaster 
      University, Lancaster, LA1 4YQ, UK.
FAU - Yuan, Li
AU  - Yuan L
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Sun, Peng
AU  - Sun P
AD  - Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 
      030001, China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 
      030001, China.
FAU - Yang, Wei
AU  - Yang W
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Wu, Mei-Na
AU  - Wu MN
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
FAU - Qi, Jin-Shun
AU  - Qi JS
AD  - Department of Physiology, Shanxi Medical University, Taiyuan 030001, China. 
      Electronic address: jinshunqi2009@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161021
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Butadienes)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitriles)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (U 0126)
RN  - 0 (amyloid beta-protein (25-35))
RN  - 74O62BB01U (lixisenatide)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amyloid beta-Peptides/*antagonists & inhibitors/pharmacology
MH  - Animals
MH  - Butadienes/pharmacology
MH  - Calcium/metabolism
MH  - Cell Survival/drug effects
MH  - Hippocampus/*drug effects
MH  - Maze Learning/drug effects
MH  - Memory, Short-Term/*drug effects
MH  - Neurons/drug effects
MH  - Neuroprotective Agents/pharmacology
MH  - Nitriles/pharmacology
MH  - Peptide Fragments/*antagonists & inhibitors/pharmacology
MH  - Peptides/*pharmacology
MH  - Primary Cell Culture
MH  - Rats
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Akt-MEK1/2 signal pathway
OT  - Amyloid beta protein
OT  - Cell viability
OT  - Intracellular calcium concentration
OT  - Lixisenatide
OT  - Working memory
EDAT- 2016/10/30 06:00
MHDA- 2017/11/07 06:00
CRDT- 2016/10/30 06:00
PHST- 2016/08/19 00:00 [received]
PHST- 2016/10/17 00:00 [revised]
PHST- 2016/10/20 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/11/07 06:00 [medline]
PHST- 2016/10/30 06:00 [entrez]
AID - S0166-4328(16)30892-0 [pii]
AID - 10.1016/j.bbr.2016.10.033 [doi]
PST - ppublish
SO  - Behav Brain Res. 2017 Feb 1;318:28-35. doi: 10.1016/j.bbr.2016.10.033. Epub 2016 
      Oct 21.