Evidence map›Paper›PMID 36084029›Full record

ArticlePloS one2022

A potent and selective inhibitor for the modulation of MAGL activity in the neurovasculature.

Alicia M Kemble, Benoit Hornsperger, Iris Ruf, Hans Richter, Jörg Benz, Bernd Kuhn, Dominik Heer, Matthias Wittwer, Britta Engelhardt, Uwe Grether and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 17% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026
    Review
  6. Article
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

11 authors at 2 institutions in 1 country.

Alicia M KembleRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.ORCID 0000-0002-8503-4474
Benoit HornspergerRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Iris RufRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Hans RichterRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Jörg BenzRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Bernd KuhnRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Dominik HeerRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Matthias WittwerRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.ORCID 0000-0003-1359-4795
Britta EngelhardtTheodor Kocher Institute, University of Bern, Bern, Switzerland.
Uwe GretherRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Ludovic CollinRoche Pharma Research & Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.ORCID 0000-0002-6313-3244
Roche (Switzerland) · CHUniversity of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic inflammation and blood-brain barrier dysfunction are key pathological hallmarks of neurological disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Major drivers of these pathologies include pro-inflammatory stimuli such as prostaglandins, which are produced in the central nervous system by the oxidation of arachidonic acid in a reaction catalyzed by the cyclooxygenases COX1 and COX2. Monoacylglycerol lipase hydrolyzes the endocannabinoid signaling lipid 2-arachidonyl glycerol, enhancing local pools of arachidonic acid in the brain and leading to cyclooxygenase-mediated prostaglandin production and neuroinflammation. Monoacylglycerol lipase inhibitors were recently shown to act as effective anti-inflammatory modulators, increasing 2-arachidonyl glycerol levels while reducing levels of arachidonic acid and prostaglandins, including PGE2 and PGD2. In this study, we characterized a novel, highly selective, potent and reversible monoacylglycerol lipase inhibitor (MAGLi 432) in a mouse model of lipopolysaccharide-induced blood-brain barrier permeability and in both human and mouse cells of the neurovascular unit: brain microvascular endothelial cells, pericytes and astrocytes. We confirmed the expression of monoacylglycerol lipase in specific neurovascular unit cells in vitro, with pericytes showing the highest expression level and activity. However, MAGLi 432 did not ameliorate lipopolysaccharide-induced blood-brain barrier permeability in vivo or reduce the production of pro-inflammatory cytokines in the brain. Our data confirm monoacylglycerol lipase expression in mouse and human cells of the neurovascular unit and provide the basis for further cell-specific analysis of MAGLi 432 in the context of blood-brain barrier dysfunction caused by inflammatory insults.

Indexed as

LipopolysaccharidesMonoacylglycerol LipasesAnimalsArachidonic AcidCyclooxygenase 2EndocannabinoidsEndothelial CellsEnzyme InhibitorsGlycerolHumansMiceMonoglyceridesProstaglandinsArachidonic AcidCyclooxygenase 2EndocannabinoidsEnzyme InhibitorsGlycerolLipopolysaccharidesMonoacylglycerol LipasesMonoglyceridesProstaglandins

Identifiers

PMID36084029
PMCPMC9462760
OpenAlexW4295048059

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.