Evidence map›Paper›PMID 38563877›Full record

ArticleInflammation2024

VCP Inhibition Augments NLRP3 Inflammasome Activation.

Ankita Sharma, Dhruva D Dhavale, Paul T Kotzbauer, Conrad C Weihl

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

Article in Inflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. In-vivo evidence of synucleinopathy in parkinsonism due to VCP mutation.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Article
  2. Review
  3. 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

4 authors at 1 institution in 1 country.

Ankita SharmaDepartment of Neurology, Hope Center for Neurological Diseases, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Dhruva D DhavaleDepartment of Neurology, Hope Center for Neurological Diseases, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Paul T KotzbauerDepartment of Neurology, Hope Center for Neurological Diseases, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Conrad C WeihlDepartment of Neurology, Hope Center for Neurological Diseases, Washington University School of Medicine, St. Louis, MO, 63110, USA. weihlc@wustl.edu.
Hope Center for Neurological Disorders · US

Funding

VCP in myopathy and dementiaR01AG031867 · NIA · WASHINGTON UNIVERSITY · PI CONRAD C WEIHL · 2009 to 2026
$9.1M
Protein Aggregation and Neurotransmitter Deficits in Parkinson DiseaseR01NS097799 · NINDS · WASHINGTON UNIVERSITY · PI PAUL T KOTZBAUER · 2016 to 2026
$5.8M
Structural Biology of Alpha-Synuclein in Lewy Body DementiaRF1NS110436 · NINDS · WASHINGTON UNIVERSITY · PI KOTZBAUER, PAUL T, RIENSTRA, CHAD M · 2023 to 2023
$4.2M
STRUCTURAL BIOLOGY OF ALPHA-SYNUCLEIN IN LEWY BODY DEMENTIAU01NS110436 · NINDS · WASHINGTON UNIVERSITY · PI KOTZBAUER, PAUL T · 2018 to 2022
$4.1M
Clinical and Translational Studies in Muscle DiseaseK24AR073317 · NIAMS · WASHINGTON UNIVERSITY · PI CONRAD C WEIHL · 2018 to 2026
$1.6M
Structural Biology of Alpha-Synuclein in Lewy Body DementiaR01NS110436 · NINDS · WASHINGTON UNIVERSITY · PI PAUL T KOTZBAUER, ELIZABETH R WRIGHT · 2026 to 2026
$1.4M
NIAMS NIH HHS K24 AR073317NIAMS NIH HHS K24AR073317NIA NIH HHS R01 AG031867NIA NIH HHS R01AG031867NIH HHS NS110436NINDS NIH HHS R01 NS097799NINDS NIH HHS RF1 NS110436NINDS NIH HHS U01 NS110436
6 · The paper itself

Abstract

Lysosomal membrane permeabilization caused either via phagocytosis of particulates or the uptake of protein aggregates can trigger the activation of NLRP3 inflammasome- an intense inflammatory response that drives the release of the pro-inflammatory cytokine IL-1β by regulating the activity of CASPASE 1. The maintenance of lysosomal homeostasis and lysosomal membrane integrity is facilitated by the AAA+ ATPase, VCP/p97 (VCP). However, the relationship between VCP and NLRP3 inflammasome activity remains unexplored. Here, we demonstrate that the VCP inhibitors, DBeQ and ML240 elicit the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) when used as activation stimuli. Moreover, genetic inhibition of VCP or VCP chemical inhibition enhances lysosomal membrane damage and augments LLoME-associated NLRP3 inflammasome activation in BMDMs. Similarly, VCP inactivation also augments NLRP3 inflammasome activation mediated by aggregated alpha-synuclein fibrils and lysosomal damage. These data suggest that VCP is a participant in the complex regulation of NLRP3 inflammasome activation.

Indexed as

InflammasomesLysosomesNLR Family, Pyrin Domain-Containing 3 ProteinValosin Containing ProteinAnimalsFuransIndenesMacrophagesMiceSulfonamidesFuransIndenesInflammasomesN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseSulfonamidesValosin Containing ProteinAlpha-synuclein fibrilsASC speckBone marrow-derived macrophagesLLoMeNLRP3 inflammasomeTAT-Cre recombinase.VCP/p97

Identifiers

PMID38563877
PMCPMC12168470
OpenAlexW4393443002

What OpenQuestion 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 OpenQuestion graph.