Neuroprotective and anti-apoptotic effects of Liraglutide on SH-SY5Y cells exposed to Methylglyoxal stress

Sharma, Mohit and Jalewa, Jaishree and Hölscher, Christian (2014) Neuroprotective and anti-apoptotic effects of Liraglutide on SH-SY5Y cells exposed to Methylglyoxal stress. Journal of Neurochemistry, 128 (3). pp. 459-471. ISSN 0022-3042

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Abstract

Glucagon-like peptide 1 (GLP-1) is a growth factor that has demonstrated neuroprotective properties in a range of studies. In an APPswe/PS1ΔE9 mouse model of Alzheimer's disease (AD), we previously found protective effects on memory formation, synaptic plasticity, synapse survival and a reduction of amyloid synthesis and plaque load in the brain. Here, we analyse the neuroprotective properties of the GLP-1 analogue liraglutide in human neuroblastoma cell line SH-SY5Y during methyl glyoxal stress. We show for the first time that cell viability was enhanced by liraglutide (XTT assay) in a dose-dependent way, while cytotoxicity (LDH assay) and apoptosis were reduced. Expression of the pro-survival Mcl1 signaling protein was increased, as was activation of cell survival kinases Akt, MEK1/2 and the transcription factor p90RSK. Liraglutide also decreased pro-apoptotic Bax and Bik expression. In addition, the membrane potential and the influx of calcium into the cell were enhanced by liraglutide. GLP-1 receptor expression was also increased by the drug. The results demonstrate a range of growth factor-related cytoprotective processes induced by liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victoza®). It is also tested in clinical trials in patients with Alzheimer disease.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Neurochemistry
Additional Information:
© 2013 International Society for Neurochemistry.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1303
Subjects:
ID Code:
67566
Deposited By:
Deposited On:
18 Nov 2013 10:31
Refereed?:
Yes
Published?:
Published
Last Modified:
16 Nov 2020 05:36