Evidence map›Paper›PMID 39796582›Full record

ArticleNutrients2024

DAG-MAG-ΒHB: A Novel Ketone Diester Modulates NLRP3 Inflammasome Activation in Microglial Cells in Response to Beta-Amyloid and Low Glucose AD-like Conditions.

Valentina Gentili, Giovanna Schiuma, Latha Nagamani Dilliraj, Silvia Beltrami, Sabrina Rizzo, Djidjell Lara, Pier Paolo Giovannini, Matteo Marti, Daria Bortolotti, Claudio Trapella and 2 more

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In one paragraph

Article in Nutrients, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
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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

12 authors.

Valentina GentiliDepartment of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0003-4572-5497
Giovanna SchiumaDepartment of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0003-4652-5550
Latha Nagamani DillirajDepartment of Chemical, Pharmaceutical, Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy.
Silvia BeltramiDepartment of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0002-5923-9265
Sabrina RizzoDepartment of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0002-9246-136X
Djidjell LaraDepartment of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0002-3088-5466
Pier Paolo GiovanniniDepartment of Chemical, Pharmaceutical, Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy.
Matteo MartiDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0001-8751-2882
Daria BortolottiDepartment of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0003-4496-9561
Claudio TrapellaDepartment of Chemical, Pharmaceutical, Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0002-6666-143X
Marco NarducciDepartment of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.
Roberta RizzoDepartment of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0001-9507-9126

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA neuroinflammatory disease such as Alzheimer's disease, presents a significant challenge in neurotherapeutics, particularly due to the complex etiology and allostatic factors, referred to as CNS stressors, that accelerate the development and progression of the disease. These CNS stressors include cerebral hypo-glucose metabolism, hyperinsulinemia, mitochondrial dysfunction, oxidative stress, impairment of neuronal autophagy, hypoxic insults and neuroinflammation. This study aims to explore the efficacy and safety of DAG-MAG-ΒHB, a novel ketone diester, in mitigating these risk factors by sustaining therapeutic ketosis, independent of conventional metabolic pathways.

methodsWe evaluated the intestinal absorption of DAG-MAG-ΒHB and the metabolic impact in human microglial cells. Utilizing the HMC3 human microglia cell line, we examined the compound's effect on cellular viability, Acetyl-CoA and ATP levels, and key metabolic enzymes under hypoglycemia. Additionally, we assessed the impact of DAG-AG-ΒHB on inflammasome activation, mitochondrial activity, ROS levels, inflammation and phagocytic rates.

resultsDAG-MAG-ΒHB showed a high rate of intestinal absorption and no cytotoxic effect. In vitro, DAG-MAG-ΒHB enhanced cell viability, preserved morphological integrity, and maintained elevated Acetyl-CoA and ATP levels under hypoglycemic conditions. DAG-MAG-ΒHB increased the activity of BDH1 and SCOT, indicating ATP production via a ketolytic pathway. DAG-MAG-ΒHB showed remarkable resilience against low glucose condition by inhibiting NLRP3 inflammasome activation.

conclusionsIn summary, DAG-MAG-ΒHB emerges as a promising treatment for neuroinflammatory conditions. It enhances cellular health under varying metabolic states and exhibits neuroprotective properties against low glucose conditions. These attributes indicate its potential as an effective component in managing neuroinflammatory diseases, addressing their complex progression.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesGlucoseInflammasomesKetonesMicrogliaNLR Family, Pyrin Domain-Containing 3 ProteinCell LineCell SurvivalHumansMitochondriaReactive Oxygen SpeciesAmyloid beta-PeptidesGlucoseInflammasomesKetonesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanReactive Oxygen SpeciesAlzheimer’s diseaseblood–brain barrierDAG-MAG-ΒHBexogenous ketonesketone diesterneuroprotectiontherapeutic ketosis

Identifiers

PMID39796582
PMCPMC11722608

What Socratic holds

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LicenceCC BY
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.