Evidence map›Paper›PMID 34569615›Full record

ArticleJournal of neurochemistry2021

The metabolite GLP-1 (9-36) is neuroprotective and anti-inflammatory in cellular models of neurodegeneration.

Yazhou Li, Elliot J Glotfelty, Tobias Karlsson, Lowella V Fortuno, Brandon K Harvey, Nigel H Greig

Open access · greenAbstract read
In one paragraph

Article in Journal of neurochemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Yazhou LiDrug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.ORCID 0000-0002-6048-3660
Elliot J GlotfeltyDrug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.ORCID 0000-0001-5125-8720
Tobias KarlssonDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-9919-3353
Lowella V FortunoMolecular Mechanisms of Cellular Stress and Inflammation Unit, Integrative Neuroscience Department, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.
Brandon K HarveyMolecular Mechanisms of Cellular Stress and Inflammation Unit, Integrative Neuroscience Department, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.ORCID 0000-0002-4036-1383
Nigel H GreigDrug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.ORCID 0000-0002-3032-1468
National Institutes of Health · USKarolinska Institutet · SE

Funding

Neuroprotective role of GLP-1 receptor agonists (Neurodegenerative disorders & Alzheimer's disease)ZIAAG000333 · NIA · NATIONAL INSTITUTE ON AGING · PI GREIG, NIGEL H. · 2009 to 2025
$10.9M
Intramural NIH HHS ZIA AG000333
6 · The paper itself

Abstract

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.

Indexed as

AnimalsAnti-Inflammatory AgentsCell Line, TransformedCell Line, TumorCells, CulturedCoculture TechniquesDose-Response Relationship, DrugFemaleGlucagon-Like Peptide 1HumansMiceMicrogliaNeurodegenerative DiseasesNeuroprotective AgentsPregnancyRatsAnti-Inflammatory AgentsGlucagon-Like Peptide 1glucagon-like peptide-1 (9-36)-amideNeuroprotective Agentsexendin-4GLP-1GLP-1 (9-36)neurodegenerationneuroinflammationneuroprotection

Identifiers

PMID34569615
PMCPMC8627453
OpenAlexW3203222544

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.