Evidence map›Paper›PMID 33257576›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer's disease.

Niklas Lonnemann, Shirin Hosseini, Carlo Marchetti, Damaris B Skouras, Davide Stefanoni, Angelo D'Alessandro, Charles A Dinarello, Martin Korte

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.

0numbers the graph read from it
0cells of the map it votes in
192citing papers in PubMed
9.4field-weighted citation impact, top 1% 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

192 citing papers in PubMed, 275 citations in OpenAlex.

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132 more citing papers are in PubMed but not listed here.

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

8 authors at 5 institutions in 3 countries.

Niklas LonnemannDepartment of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany.ORCID 0000-0002-7285-9995
Shirin HosseiniDepartment of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany.ORCID 0000-0001-7949-862X
Carlo MarchettiDepartment of Medicine, University of Colorado, Denver, Aurora, CO 80045.ORCID 0000-0002-0203-316X
Damaris B SkourasR&D Division, Olatec Therapeutics, New York, NY 10065.
Davide StefanoniDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver, Aurora, CO 80045.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver, Aurora, CO 80045.ORCID 0000-0002-2258-6490
Charles A DinarelloDepartment of Medicine, University of Colorado, Denver, Aurora, CO 80045; cdinare333@aol.com m.korte@tu-bs.de.ORCID 0000-0002-5073-8316
Martin KorteDepartment of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany; cdinare333@aol.com m.korte@tu-bs.de.ORCID 0000-0001-6956-5913
University of Colorado Denver · USHelmholtz Centre for Infection Research · DEOlatec (United States) · USRadboud University Nijmegen · NLTechnische Universität Braunschweig · DE

Funding

Yeast-based HTS Assay Technologies for ProteasesR01AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1985 to 2025
$8.5M
Pathogenesis of Fever in ManR56AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 2016 to 2016
$311k
NIAID NIH HHS R01 AI015614NIAID NIH HHS R56 AI015614
6 · The paper itself

Abstract

Numerous studies demonstrate that neuroinflammation is a key player in the progression of Alzheimer's disease (AD). Interleukin (IL)-1β is a main inducer of inflammation and therefore a prime target for therapeutic options. The inactive IL-1β precursor requires processing by the the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome into a mature and active form. Studies have shown that IL-1β is up-regulated in brains of patients with AD, and that genetic inactivation of the NLRP3 inflammasome improves behavioral tests and synaptic plasticity phenotypes in a murine model of the disease. In the present study, we analyzed the effect of pharmacological inhibition of the NLRP3 inflammasome using dapansutrile (OLT1177), an oral NLRP3-specific inhibitor that is safe in humans. Six-month-old WT and APP/PS1 mice were fed with standard mouse chow or OLT1177-enriched chow for 3 mo. The Morris water maze test revealed an impaired learning and memory ability of 9-mo-old APP/PS1 mice (

Indexed as

Administration, OralAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsBehavior, AnimalBehavior Observation TechniquesCerebral CortexCognitive DysfunctionDisease Models, AnimalHumansInflammasomesMaleMiceMice, TransgenicMicrogliaNeuronal PlasticityAmyloid beta-Protein PrecursorAPP protein, mousedapansutrileInflammasomesNitrilesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePresenilin-1presenilin 1, mouseSulfonesAlzheimer’s disease synapticcognitive functionsynaptic plasticity

Identifiers

PMID33257576
PMCPMC7749353
OpenAlexW3108308610

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.