ArticleActa neuropathologica2015
Isoglutaminyl cyclase contributes to CCL2-driven neuroinflammation in Alzheimer's disease.
Article in Acta neuropathologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study.Alzheimer's research & therapy · 2018Trial
- Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.Experimental & molecular medicine · 2026Review
- Chemokines in Alzheimer's Disease: Early Defence, Late Damage and the Impact of Sex and Infection.Basic & clinical pharmacology & toxicology · 2026Review
- Exploring the Expression Changes of Immune Genes in Alzheimer's Disease: A Study on ANXA1, VCAM1, and CCL2.Molecular neurobiology · 2026Article
- Immunomodulatory functions of glutaminyl cyclases QPCTL and QPCT.Frontiers in immunology · 2026Review
- Ocular neuroinflammatory response secondary to SARS-CoV-2 infection-a review.Frontiers in immunology · 2025Review
- Article
- Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer's disease.BMC medical genomics · 2023Article
- Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings.Molecular psychiatry · 2023Article
- Glial Cell-Mediated Neuroinflammation in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Role of Chemokines in the Development and Progression of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2022Review
- Peptide backbone modifications of amyloid β (1-40) impact fibrillation behavior and neuronal toxicity.Scientific reports · 2021Article
- Innate immunity stimulation via CpG oligodeoxynucleotides ameliorates Alzheimer's disease pathology in aged squirrel monkeys.Brain : a journal of neurology · 2021Article
- Targeting the CCL2-CCR2 axis in depressive disorders.Pharmacological reports : PR · 2021Review
- Cerebrospinal Fluid Biomarkers of Alzheimer's Disease: Current Evidence and Future Perspectives.Brain sciences · 2021Review
- Gene Set Index Based on Different Modules May Help Differentiate the Mechanisms of Alzheimer's Disease and Vascular Dementia.Clinical interventions in aging · 2021Article
- Regulation and biological functions of the CX3CL1-CX3CR1 axis and its relevance in solid cancer: A mini-review.Journal of Cancer · 2021Review
- Atypical chemokine receptor ACKR2-V41A has decreased CCL2 binding, scavenging, and activation, supporting sustained inflammation and increased Alzheimer's disease risk.Scientific reports · 2020Article
- Endogenous mouse huntingtin is highly abundant in cranial nerve nuclei, co-aggregates to Abeta plaques and is induced in reactive astrocytes in a transgenic mouse model of Alzheimer's disease.Acta neuropathologica communications · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The brains of Alzheimer's disease (AD) patients are characterized by deposits of Abeta peptides and by accompanying chronic inflammation. Here, we provide evidence that the enzyme isoglutaminyl cyclase (isoQC) is a novel factor contributing to both aspects of AD pathology. Two putative substrates of isoQC, N-truncated Abeta peptides and the monocyte chemoattractant chemokine CCL2, undergo isoQC-catalyzed pyroglutamate (pGlu) modification. This triggers Abeta aggregation and facilitates the biological activity of CCL2, which collectively results in the formation of high molecular weight Abeta aggregates, glial cell activation, neuroinflammation and neuronal cell death. In mouse brain, we found isoQC to be neuron-specifically expressed in neocortical, hippocampal and subcortical structures, localized to the endoplasmic reticulum and Golgi apparatus as well as co-expressed with its substrate CCL2. In aged APP transgenic Tg2576 mice, both isoQC and CCL2 mRNA levels are up-regulated and isoQC and CCL2 proteins were found to be co-induced in Abeta plaque-associated reactive astrocytes. Also, in mouse primary astrocyte culture, a simultaneous up-regulation of isoQC and CCL2 expression was revealed upon Abeta and pGlu-Abeta stimulation. In brains of AD patients, the expression of isoQC and CCL2 mRNA and protein is up-regulated compared to controls and correlates with pGlu-Abeta load and with the decline in mini-mental state examination. Our observations provide evidence for a dual involvement of isoQC in AD pathogenesis by catalysis of pGlu-Abeta and pGlu-CCL2 formation which mutually stimulate inflammatory events and affect cognition. We conclude that isoQC inhibition may target both major pathological events in the development of AD.
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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.