ArticleThe Journal of clinical investigation2021
Complement C3a receptor-mediated vascular dysfunction: a complex interplay between aging and neurodegeneration.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 38 citations in OpenAlex.
- The complement system in Alzheimer's disease: evaluating biomarker potential in a complex neuroimmune context.Journal of neuroinflammation · 2026Review
- Complement 3a Receptor mediates high fat diet induced hypothalamic accumulation of lipid associated microglia to regulate neuroinflammation and obesity.bioRxiv : the preprint server for biology · 2026Article
- Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Circulating cfdna: A novel biomarker for preventing early recurrence in ischemic stroke.Journal of thrombosis and thrombolysis · 2026Review
- Neuroinflammation and blood-brain barrier dysfunction in cerebral small vessel disease: mechanisms, biomarkers, and therapeutic implications.European journal of medical research · 2026Review
- The immune-endothelial axis in neurovascular pathophysiology: a framework for targeted interventions.Frontiers in immunology · 2026Review
- Effects of Long-Term Moderate-Intensity Exercise on Autonomic Nervous System Dysfunction Induced by Cardiac Neurovascular Interface Deterioration.Reviews in cardiovascular medicine · 2025Review
- Knockdown of C3aR alleviates age-related bone loss via activation of YAP1/β-catenin signaling.The Journal of biological chemistry · 2025Article
- Complement C3/C3aR Signaling Pathway Inhibition Ameliorates Retinal Damage in Experimental Retinal Vein Occlusion.Investigative ophthalmology & visual science · 2025Article
- Complement C3/C3aR Signaling Pathway Inhibition Ameliorates Retinal Damage in Experimental Retinal Vein Occlusion.Investigative ophthalmology & visual science · 2025Article
- Knockdown of C3aR alleviates age-related bone loss via activation of YAP1/β-catenin signaling.The Journal of biological chemistry · 2025Article
- Structural insights into the agonist activity of the nonpeptide modulator JR14a on C3aR.Cell discovery · 2025Article
- The Role of Extracellular Vesicles and Microparticles in Central Nervous System Disorders: Mechanisms, Biomarkers, and Therapeutic Potential.Cellular and molecular neurobiology · 2024Review
- Acute depletion of complement C3 with cobra venom factor attenuates memory deficits induced by status epilepticus.Epilepsia open · 2024Article
- Research Progress on Natural Plant Molecules in Regulating the Blood-Brain Barrier in Alzheimer's Disease.Molecules (Basel, Switzerland) · 2023Review
- Review
- Role of neuroinflammation in neurodegeneration development.Signal transduction and targeted therapy · 2023Review
- Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation.EMBO reports · 2023Article
- Endothelial Glycocalyx and Cardiomyocyte Damage Is Prevented by Recombinant Syndecan-1 in Acute Myocardial Infarction.The American journal of pathology · 2023Article
- Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments.Stroke · 2023Review
Corrections and comments
- Comment on
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular dysfunction resulting in compromised blood-brain barrier (BBB) integrity is evident in aging and disease. Although the complement C3a/C3a receptor (C3a/C3aR) axis influences normal brain aging and disease progression, the mechanisms governing endothelial C3aR-mediated neurovascular inflammation and BBB permeability remain unexplored. In this issue of the JCI, Propson et al. investigated endothelial C3a/C3aR signaling in normal, aged, and neurodegenerative mouse models. Endothelial C3aR signaling modulated age-dependent increases in VCAM1, initiated peripheral lymphocyte infiltration, and enhanced microglial activity. Increased calcium release downstream of C3aR signaling disrupted the vascular endothelial cadherin (VE-cadherin) junctions, increased BBB permeability, and degraded vascular structure and function. Mice lacking C3aR (C3ar1-/-) and mice treated with a C3aR antagonist showed attenuated age-related microglial reactivity and neurodegeneration. These results confirm that complement-mediated signaling impacts vascular health and BBB function in normal aging and neurodegenerative disease, suggesting that complement inhibitors represent a therapeutic option for cerebral microvascular dysfunction.
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.