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.
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Authors | Mohit K Sharma, Jaishree Jalewa, Christian Hölscher |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 128
Issue 3
Pg. 459-71
(Feb 2014)
ISSN: 1471-4159 [Electronic] England |
PMID | 24112036
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 International Society for Neurochemistry. |
Chemical References |
- Apoptosis Regulatory Proteins
- BIK protein, human
- GLP1R protein, human
- Glp1r protein, mouse
- Glucagon-Like Peptide-1 Receptor
- Hypoglycemic Agents
- Membrane Proteins
- Mitochondrial Proteins
- Neuroprotective Agents
- Receptors, Glucagon
- bcl-2-Associated X Protein
- Pyruvaldehyde
- Liraglutide
- Glucagon-Like Peptide 1
- Oncogene Protein v-akt
- Mitogen-Activated Protein Kinases
- Caspase 3
- Calcium
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Topics |
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
(metabolism)
- Blotting, Western
- Calcium
(metabolism)
- Caspase 3
(metabolism)
- Cell Line
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Glucagon-Like Peptide 1
(analogs & derivatives, pharmacology)
- Glucagon-Like Peptide-1 Receptor
- Humans
- Hypoglycemic Agents
(pharmacology)
- Immunohistochemistry
- Liraglutide
- Membrane Potentials
- Membrane Proteins
(metabolism)
- Mitochondrial Proteins
- Mitogen-Activated Protein Kinases
(metabolism)
- Neuroprotective Agents
- Oncogene Protein v-akt
(metabolism)
- Pyruvaldehyde
(toxicity)
- Receptors, Glucagon
(biosynthesis, genetics)
- Stress, Physiological
(drug effects)
- bcl-2-Associated X Protein
(metabolism)
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