ArticleEMBO molecular medicine2011
The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions.
Article in EMBO molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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.
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.
Who cites it
41 citing papers in PubMed, 91 citations in OpenAlex.
- Proteomic profiling in cerebrospinal fluid reveal biomarkers for shunt outcome in idiopathic normal-pressure hydrocephalus.Journal of advanced research · 2026Article
- Immunomodulatory functions of glutaminyl cyclases QPCTL and QPCT.Frontiers in immunology · 2026Review
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- Article
- Adipocyte-Specific Hnrnpa1 Knockout Aggravates Obesity-Induced Metabolic Dysfunction via Upregulation of CCL2.Diabetes · 2024Article
- Development of lactoferrin-coated multifunctional copolymer micelles to cross the blood-brain barrier.Drug delivery and translational research · 2024Article
- Mural cell-derived chemokines provide a protective niche to safeguard vascular macrophages and limit chronic inflammation.Immunity · 2023Article
- Deciphering the role of QPCTL in glioma progression and cancer immunotherapy.Frontiers in immunology · 2023Article
- Development and evolution of human glutaminyl cyclase inhibitors (QCIs): an alternative promising approach for disease-modifying treatment of Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery.International journal of obesity (2005) · 2022Article
- 2-Amino-1,3,4-thiadiazoles as Glutaminyl Cyclases Inhibitors Increase Phagocytosis through Modification of CD47-SIRPα Checkpoint.ACS medicinal chemistry letters · 2022Article
- Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity.Nature immunology · 2022Article
- Modulating the tumor-associated macrophage landscape.Nature immunology · 2022Article
- Pyroglutamate Aβ cascade as drug target in Alzheimer's disease.Molecular psychiatry · 2022Review
- The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs.Pulmonary therapy · 2022Article
- QPCTL regulates macrophage and monocyte abundance and inflammatory signatures in the tumor microenvironment.Oncoimmunology · 2022Article
- Upregulation of Glutaminyl Cyclase Contributes to ERS-Induced Apoptosis in PC12 Cells.BioMed research international · 2022Article
- Combination of the Glutaminyl Cyclase Inhibitor PQ912 (Varoglutamstat) and the Murine Monoclonal Antibody PBD-C06 (m6) Shows Additive Effects on Brain Aβ Pathology in Transgenic Mice.International journal of molecular sciences · 2021Article
- Repurposing FDA-Approved Compounds for the Discovery of Glutaminyl Cyclase Inhibitors as Drugs Against Alzheimer's Disease.ChemistryOpen · 2021Article
- From ELISA to Immunosorbent Tandem Mass Spectrometry Proteoform Analysis: The Example of CXCL8/Interleukin-8.Frontiers in immunology · 2021Article
Corrections and comments
- Commented on by
Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute and chronic inflammatory disorders are characterized by detrimental cytokine and chemokine expression. Frequently, the chemotactic activity of cytokines depends on a modified N-terminus of the polypeptide. Among those, the N-terminus of monocyte chemoattractant protein 1 (CCL2 and MCP-1) is modified to a pyroglutamate (pE-) residue protecting against degradation in vivo. Here, we show that the N-terminal pE-formation depends on glutaminyl cyclase activity. The pE-residue increases stability against N-terminal degradation by aminopeptidases and improves receptor activation and signal transduction in vitro. Genetic ablation of the glutaminyl cyclase iso-enzymes QC (QPCT) or isoQC (QPCTL) revealed a major role of isoQC for pE(1) -CCL2 formation and monocyte infiltration. Consistently, administration of QC-inhibitors in inflammatory models, such as thioglycollate-induced peritonitis reduced monocyte infiltration. The pharmacologic efficacy of QC/isoQC-inhibition was assessed in accelerated atherosclerosis in ApoE3*Leiden mice, showing attenuated atherosclerotic pathology following chronic oral treatment. Current strategies targeting CCL2 are mainly based on antibodies or spiegelmers. The application of small, orally available inhibitors of glutaminyl cyclases represents an alternative therapeutic strategy to treat CCL2-driven disorders such as atherosclerosis/restenosis and fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.