ArticleProceedings of the National Academy of Sciences of the United States of America2012
C3-dependent mechanism of microglial priming relevant to multiple sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled 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.
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
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- The Crossroads of Neuroinflammation and Biomarkers in Multiple Sclerosis: A Systematic Review.Cells · 2026Pooled it
- Trained immunity: induction of an inflammatory memory in disease.Cell research · 2025Review
- Early antiviral treatment following gammaherpesvirus-68 infection of the central nervous system prevents subsequent multiple sclerosis-like disease.Journal of neuroinflammation · 2025Article
- Review
- Neuroinflammation: Mechanisms, Dual Roles, and Therapeutic Strategies in Neurological Disorders.Current issues in molecular biology · 2025Review
- Analysis and interpretation of inflammatory fluid markers in Alzheimer's disease: a roadmap for standardization.Journal of neuroinflammation · 2025Review
- Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis.Frontiers in immunology · 2025Article
- Innate immune memory in chronic HIV and HIV-associated neurocognitive disorders (HAND): potential mechanisms and clinical implications.Journal of neurovirology · 2024Review
- Purinergic exposure induces epigenomic and transcriptomic-mediated preconditioning resembling epilepsy-associated microglial states.iScience · 2024Article
- Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons.Cell stem cell · 2024Article
- EF1α-associated protein complexes affect dendritic spine plasticity by regulating microglial phagocytosis in Fmr1 knock-out mice.Molecular psychiatry · 2024Article
- The Immunometabolic Gene N-Acetylglucosamine Kinase Is Uniquely Involved in the Heritability of Multiple Sclerosis Severity.International journal of molecular sciences · 2024Article
- Complement Activation Is Associated With Disease Severity in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation.Nature communications · 2024Article
- Transient Receptor Potential Vanilloid 4-Dependent Microglial Function in Myelin Injury and Repair.International journal of molecular sciences · 2023Article
- Noteworthy perspectives on microglia in neuropsychiatric disorders.Journal of neuroinflammation · 2023Review
- Mesenchymal-derived extracellular vesicles enhance microglia-mediated synapse remodeling after cortical injury in aging Rhesus monkeys.Journal of neuroinflammation · 2023Article
- Roles and regulation of microglia activity in multiple sclerosis: insights from animal models.Nature reviews. Neuroscience · 2023Review
- GSDMD in peripheral myeloid cells regulates microglial immune training and neuroinflammation in Parkinson's disease.Acta pharmaceutica Sinica. B · 2023Article
- Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases.Neural regeneration research · 2022Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Microglial priming predisposes the brain to neurodegeneration and affects disease progression. The signal to switch from the quiescent to the primed state is unknown. We show that deleting the C3 convertase regulator complement receptor 1-related protein y (Crry) induces microglial priming. Mice that were double-knockout for Crry and either C3 or factor B did not show priming, demonstrating dependence on alternative pathway activation. Colocalization of C3b/iC3b and CR3 implicated the CR3/iC3b interaction in priming. Systemic lipopolysaccharide challenge overactivated primed microglia with florid expression of proinflammatory molecules, which were blocked by complement inhibition. Relevance for neurodegenerative disease is exemplified by human multiple sclerosis (MS) and by experimental autoimmune encephalomyelitis (EAE), a model of MS. In human MS, microglial priming was evident in perilesional white matter, in close proximity to C3b/iC3b deposits. EAE was accelerated and exacerbated in Crry-deficient mice, and was dependent on C activation. In summary, C3-dependent microglial priming confers susceptibility to other challenges. Our observations are relevant to progression in MS and other neurological diseases exacerbated by acute insults.
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.