ArticleMolecular neurodegeneration2017
Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- CD11c + microglia: From basic research to clinical application.Neural regeneration research · 2026Article
- Article
- Targeting Microglial C5aR1 with PMX205 Attenuates Neuroinflammation and Improves Neurological Recovery After Intracerebral Hemorrhage.Neurochemical research · 2026Article
- Senescent cells in systemic aging: SASP heterogeneity, immune escape, and endocrine modulation.Biogerontology · 2026Review
- C5aR1 Inhibition Alleviates Cranial Radiation-Induced Cognitive Decline.Cancer research · 2026Article
- Differential downstream signaling in microglia lacking Alzheimer's-related TREM2 or its adaptor TYROBP/DAP12.Molecular neurodegeneration advances · 2026Article
- Emerging pathological mechanisms of Alzheimer's disease pathogenesis: from neuroimmune interactions to intercellular communication.Frontiers in aging neuroscience · 2026Review
- Remodeling of the brain immune microenvironment in Alzheimer's disease: interactions among microglia, astrocytes, complement, and the neurovascular unit.Frontiers in immunology · 2026Review
- Neurovascular Dysfunction and Glymphatic Impairment: An Unexplored Therapeutic Frontier in Neurodegeneration.International journal of molecular sciences · 2025Review
- Complement pathway dysregulation and astrocyte alterations in Down syndrome: evidence from postmortem brain tissue and iPSC-derived astrocytes.Acta neuropathologica communications · 2025Article
- Atomoxetine Drug Properties for Repurposing as a Candidate Alzheimer's Disease Therapeutic Agent.ACS pharmacology & translational science · 2025Review
- The Crosstalk Between Sepsis-Associated Encephalopathy and Alzheimer's Disease: Identifying Potential Biomarkers and Therapeutic Targets for Cognition.Molecular neurobiology · 2025Article
- Redox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Young adult microglial deletion of C1q reduces engulfment of synapses and prevents cognitive impairment in an aggressive Alzheimer's disease mouse model.bioRxiv : the preprint server for biology · 2025Article
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Exploring the intersection of atherosclerosis and Alzheimer's disease: the role of inflammation and complement activation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Immune checkpoint inhibition perturbs neuro-immune homeostasis and impairs cognitive function.Journal of experimental & clinical cancer research : CR · 2025Article
- The Alzheimer's disease-associated complement receptor 1 variant confers risk by impacting glial phagocytosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that the effect of the antagonist was specifically via C5aR1 inhibition, mice lacking C5aR1 were generated and compared in behavior and pathology. In addition, since C5aR1 is primarily expressed on cells of the myeloid lineage, and only to a lesser extent on endothelial cells and neurons in brain, gene expression in microglia isolated from adult brain at multiple ages was compared across all genotypes.
methodsC5aR1 knock out mice were crossed to the Arctic AD mouse model, and characterized for pathology and for behavior performance in a hippocampal dependent memory task. CX3CR1
resultsA lack of C5aR1 prevented behavior deficits at 10 months, although amyloid plaque load was not altered. Immunohistochemical analysis showed no CCR2
conclusionsThese data are consistent with microglial polarization in the absence of C5aR1 signaling reflecting decreased induction of inflammatory genes and enhancement of degradation/clearance pathways, which is accompanied by preservation of CA1 neuronal complexity and hippocampal dependent cognitive function. These results provide links between microglial responses and loss of cognitive performance and, combined with the previous pharmacological approach to inhibit C5aR1 signaling, support the potential of this receptor as a novel therapeutic target for AD in humans.
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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.