PMID- 35992601
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220823
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 14
DP  - 2022
TI  - Exendin-4 alleviates beta-Amyloid peptide toxicity via DAF-16 in a Caenorhabditis 
      elegans model of Alzheimer's disease.
PG  - 955113
LID - 10.3389/fnagi.2022.955113 [doi]
LID - 955113
AB  - Epidemiological analyses indicate that type 2 diabetes mellitus (T2DM) is a risk 
      factor for Alzheimer's disease (AD). They share common pathophysiological 
      mechanisms. Thus, it has been increasingly suggested that several anti-T2DM drugs 
      may have therapeutic potential in AD. Exendin-4, as a glucagon-like peptide-1 
      (GLP-1) receptor agonist, is an approved drug used to treat T2DM. In this 
      research, the neuroprotective effect of Exendin-4 was investigated for the first 
      time using transgenic Caenorhabditis elegans. Our results demonstrated that 
      Exendin-4 attenuated the amyloid-beta (1-42) (Abeta1-42) toxicity via multiple 
      mechanisms, such as depressing its expression on protein and mRNA and reducing Abeta 
      (1-42) accumulation. Exendin-4 at 0.5 mg/ml had been shown to extend life by 
      34.39% in CL4176 and delay the onset of paralysis in CL4176 and CL2006 which were 
      increased by 8.18 and 8.02%, respectively. With the treatment of Exendin-4, the 
      nuclear translocation of DAF-16 in the transgenic nematode TJ356 was enhanced. 
      Superoxide dismutase-3 (SOD-3), as a downstream target gene regulated by DAF-16, 
      was upregulated on mRNA level and activity. The reactive oxygen species (ROS) 
      level was decreased. In contrast, we observed that the ability of Exendin-4 to 
      regulate SOD was decreased in CL4176 worms with the DAF-16 gene silenced. The 
      activity of SOD and the mRNA level of sod-3 were downregulated by 30.45 and 
      43.13%, respectively. Taken together, Exendin-4 attenuated Abeta (1-42) toxicity in 
      the C. elegans model of AD via decreasing the expression and the accumulation of 
      Abeta (1-42). Exendin-4 exhibited the ability of antioxidant stress through DAF-16. 
      With continuous research, Exendin-4 would become a potential therapeutic strategy 
      for treating AD.
CI  - Copyright (c) 2022 Song, Sun, Wang, Su, Wang and Wang.
FAU - Song, Xiangwei
AU  - Song X
AD  - School of Life Sciences, Changchun Normal University, Changchun, China.
FAU - Sun, Yingqi
AU  - Sun Y
AD  - School of Life Sciences, Changchun Normal University, Changchun, China.
FAU - Wang, Zhun
AU  - Wang Z
AD  - Plant Inspection and Quarantine Laboratory, Changchun Customs Technical Center, 
      Changchun, China.
FAU - Su, Yingying
AU  - Su Y
AD  - School of Life Sciences, Changchun Normal University, Changchun, China.
FAU - Wang, Yangkun
AU  - Wang Y
AD  - School of Life Sciences, Changchun Normal University, Changchun, China.
FAU - Wang, Xueli
AU  - Wang X
AD  - School of Grain, Jilin Business and Technology College, Changchun, China.
LA  - eng
PT  - Journal Article
DEP - 20220805
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC9389237
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Amyloid-beta peptide
OT  - Caenorhabditis elegans
OT  - DAF-16
OT  - Exendin-4
OT  - neuroprotection
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/23 06:00
MHDA- 2022/08/23 06:01
PMCR- 2022/01/01
CRDT- 2022/08/22 04:30
PHST- 2022/05/28 00:00 [received]
PHST- 2022/07/11 00:00 [accepted]
PHST- 2022/08/22 04:30 [entrez]
PHST- 2022/08/23 06:00 [pubmed]
PHST- 2022/08/23 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2022.955113 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2022 Aug 5;14:955113. doi: 10.3389/fnagi.2022.955113. 
      eCollection 2022.