The metabolite GLP-1 (9-36) is neuroprotective and anti-inflammatory in cellular models of neurodegeneration
© 2021 International Society for Neurochemistry. This article has been contributed to by US Government employees and their work is in the public domain in the USA..
Glucagon-like peptide-1 (GLP-1) is best known for its insulinotropic action following food intake. Its metabolite, GLP-1 (9-36), was assumed biologically inactive because of low GLP-1 receptor (GLP-1R) affinity and non-insulinotropic properties; however, recent studies contradict this assumption. Increased use of FDA approved GLP-1 analogues for treating metabolic disorders and neurodegenerative diseases raises interest in GLP-1 (9-36)'s biological role. We use human SH-SY5Y neuroblastoma cells and a GLP-1R over-expressing variety (#9), in both undifferentiated and differentiated states, to evaluate the neurotrophic/neuroprotective effects of GLP-1 (9-36) against toxic glutamate exposure and other oxidative stress models (via the MTS, LDH or ROS assays). In addition, we examine GLP-1 (9-36)'s signaling pathways, including cyclic-adenosine monophosphate (cAMP), protein kinase-A (PKA), and 5' adenosine monophosphate-activated protein kinase (AMPK) via the use of ELISA, pharmacological inhibitors, or GLP-1R antagonist. Human HMC3 and mouse IMG microglial cell lines were used to study the anti-inflammatory effects of GLP-1 (9-36) against lipopolysaccharide (LPS) (via ELISA). Finally, we applied GLP-1 (9-36) to primary dissociation cultures challenged with α-synuclein or amyloid-β and assessed survival and morphology via immunochemistry. We demonstrate evidence of GLP-1R, cAMP, PKA, and AMPK-mediated neurotrophic and neuroprotective effects of GLP-1 (9-36). The metabolite significantly reduced IL-6 and TNF-α levels in HMC3 and IMG microglial cells, respectively. Lastly, we show mild but significant effects of GLP-1 (9-36) in primary neuron cultures challenged with α-synuclein or amyloid-β. These studies enhance understanding of GLP-1 (9-36)'s effects on the nervous system and its potential as a primary or complementary treatment in pathological contexts.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:159 |
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| Enthalten in: |
Journal of neurochemistry - 159(2021), 5 vom: 31. Dez., Seite 867-886 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Yazhou [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.01.2022 Date Revised 02.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/jnc.15521 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM331112558 |
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| 245 | 1 | 4 | |a The metabolite GLP-1 (9-36) is neuroprotective and anti-inflammatory in cellular models of neurodegeneration |
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| 520 | |a © 2021 International Society for Neurochemistry. This article has been contributed to by US Government employees and their work is in the public domain in the USA. | ||
| 520 | |a Glucagon-like peptide-1 (GLP-1) is best known for its insulinotropic action following food intake. Its metabolite, GLP-1 (9-36), was assumed biologically inactive because of low GLP-1 receptor (GLP-1R) affinity and non-insulinotropic properties; however, recent studies contradict this assumption. Increased use of FDA approved GLP-1 analogues for treating metabolic disorders and neurodegenerative diseases raises interest in GLP-1 (9-36)'s biological role. We use human SH-SY5Y neuroblastoma cells and a GLP-1R over-expressing variety (#9), in both undifferentiated and differentiated states, to evaluate the neurotrophic/neuroprotective effects of GLP-1 (9-36) against toxic glutamate exposure and other oxidative stress models (via the MTS, LDH or ROS assays). In addition, we examine GLP-1 (9-36)'s signaling pathways, including cyclic-adenosine monophosphate (cAMP), protein kinase-A (PKA), and 5' adenosine monophosphate-activated protein kinase (AMPK) via the use of ELISA, pharmacological inhibitors, or GLP-1R antagonist. Human HMC3 and mouse IMG microglial cell lines were used to study the anti-inflammatory effects of GLP-1 (9-36) against lipopolysaccharide (LPS) (via ELISA). Finally, we applied GLP-1 (9-36) to primary dissociation cultures challenged with α-synuclein or amyloid-β and assessed survival and morphology via immunochemistry. We demonstrate evidence of GLP-1R, cAMP, PKA, and AMPK-mediated neurotrophic and neuroprotective effects of GLP-1 (9-36). The metabolite significantly reduced IL-6 and TNF-α levels in HMC3 and IMG microglial cells, respectively. Lastly, we show mild but significant effects of GLP-1 (9-36) in primary neuron cultures challenged with α-synuclein or amyloid-β. These studies enhance understanding of GLP-1 (9-36)'s effects on the nervous system and its potential as a primary or complementary treatment in pathological contexts | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Harvey, Brandon K |e verfasserin |4 aut | |
| 700 | 1 | |a Greig, Nigel H |e verfasserin |4 aut | |
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