Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 6, June, p. 661–668

doi: 10.17219/acem/121007

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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The role of GLP-1/GIP receptor agonists in Alzheimer’s disease

Chun Jiang Yu1,A,B,F, Dongying Ma2,A,B,E, Ling Ling Song3,B, Zhen Nan Zhai1,B, Ye Tao4,B,C, Ying Zhang5,B,C, Ling Yu Cai6,B,C, Ya Hui Hou7,B,D, Hong Yuan Chen1,B,E, Li Wang8,A,C

1 Department of Neurology, Second Affiliated Hospital of the Harbin Medical University, China

2 Department of Neurosurgery, Second Affiliated Hospital of the Harbin Medical University, China

3 Department of Neurology, Second Hospital of Chaoyang City, China

4 Department of Neurology, First Hospital of Suihua City, China

5 Department of Neurology, People’s Hospital of Hulunbuir, China

6 Department of Neurology, 117 hospital of PLA, Hangzhou, China

7 Department of Neurology, People’s Hospital of the West Coast New District of QingDao, China

8 Department of Geriatrics, Second Affiliated Hospital of the Harbin Medical University, China


Background. New glucagon-like peptide-1 (GLP-1) analogues developed in recent years have a long half-life and offer further prospects for clinical application. At present, the neuroprotection of GLP-1 analogues in Alzheimer’s disease (AD) has just begun to be explored.
Objectives. To investigate how glucagon-like peptide-1 (liraglutide) plays a protective role in AD by regulating tau activation and BACE1 expression.
Material and Methods. Human neuroblastoma cell line SH-SY5Y cells were cultured in vitro and pretreated with different concentrations of liraglutide, and then treated with different concentrations of okadaic acid (OA) in order to observe the apoptosis of the SH-SY5Y cells. After liraglutide treatment, the apoptosis of neurons in AD rats was detected using flow cytometry, and tau activation and β-site APP cleaving enzyme 1 (BACE1) expression were detected using western blot.
Results. Different concentrations of OA were able to induce apoptosis of SH-SY5Y cells in a dose-dependent manner. Different concentrations of liraglutide were used to pretreat SH-SY5Y cells, which were able to protect the SH-SY5Y cells from apoptosis induced by OA. Okadaic acid significantly increased tau activation and BACE1 expression in the SH-SY5Y cells, which was blocked with liraglutide pretreatment. The results of a water maze experiment showed that liraglutide had significant protective effects on memory and cognitive ability in AD rats induced with OA, inhibited apoptosis of neural cells in AD rats, and inhibited tau activation and BACE1 expression of neural cells in AD rats induced with OA.
Conclusion. Liraglutide has a protective effect on AD in vivo and in vitro, which may be mediated by preventing neuronal apoptosis and inhibiting the activation of tau and the expression of BACE1.

Key words

Alzheimer’s disease, cognition, memory, nerve, glucagon-like peptide-1

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