Evidence map›Paper›PMID 39104412›Full record

ArticleiScience2024

Small molecule inhibitor binds to NOD-like receptor family pyrin domain containing 3 and prevents inflammasome activation.

Angela Lackner, Julia Elise Cabral, Yanfei Qiu, Haitian Zhou, Lemuel Leonidas, Minh Anh Pham, Alijah Macapagal, Sophia Lin, Emy Armanus, Reginald McNulty

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Angela LacknerLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Julia Elise CabralLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Yanfei QiuLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Haitian ZhouLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Lemuel LeonidasLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Minh Anh PhamLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Alijah MacapagalLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Sophia LinLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Emy ArmanusLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.
Reginald McNultyLaboratory of Macromolecular Structure, Department of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, Steinhaus Hall, Irvine, CA 92694-3900, USA.

Funding

Macromolecular assemblies of transcription factors initiated by pathogen infectionK22AI139444 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI MCNULTY, REGINALD · 2019 to 2021
$297k
NIAID NIH HHS K22 AI139444NIAID NIH HHS L30 AI140191
6 · The paper itself

Abstract

Despite recent advances in the mechanism of oxidized DNA activating NLRP3, the molecular mechanism and consequence of oxidized DNA associating with NLRP3 remains unknown. Cytosolic NLRP3 binds oxidized DNA which has been released from the mitochondria, which subsequently triggers inflammasome activation. Human glycosylase (hOGG1) repairs oxidized DNA damage which inhibits inflammasome activation. The fold of NLRP3 pyrin domain contains amino acids and a protein fold similar to hOGG1. Amino acids that enable hOGG1 to bind and cleave oxidized DNA are conserved in NLRP3. We found NLRP3 could bind and cleave oxidized guanine within mitochondrial DNA. The binding of oxidized DNA to NLRP3 was prevented by small molecule drugs which also inhibit hOGG1. These same drugs also inhibited inflammasome activation. Elucidating this mechanism will enable the design of drug memetics that treat inflammasome pathologies, illustrated herein by NLRP3 pyrin domain inhibitors which suppressed interleukin-1β (IL-1β) production in macrophages.

Indexed as

Immune responseMolecular interactionPharmacology

Identifiers

PMID39104412
PMCPMC11298654

What OpenQuestion holds

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Registered trials

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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.