ArticleNeuron2015
NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease.
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 410 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
410 citing papers in PubMed, 2 syntheses or guidelines pooled it, 683 citations in OpenAlex.
- Bibliometric analysis of neuroinflammation and Alzheimer's disease.Frontiers in aging neuroscience · 2024Pooled it
- Roles of neuropathology-associated reactive astrocytes: a systematic review.Acta neuropathologica communications · 2023Pooled it
- NF-κB across the Alzheimer disease spectrum: Context-dependent protective and pathogenic roles.IBRO neuroscience reports · 2026Review
- Early amyloid pathology in mice synergistically worsens post-sepsis behavioral impairment and microglial synaptic phagocytosis.Brain, behavior, & immunity - health · 2026Article
- Bone marrow myelopoiesis dysfunction in Alzheimer's disease limits monocyte homing to the brain and drives disease progression.Nature neuroscience · 2026Article
- Identification of Age-Associated Upstream Regulators to Promote Neuronal Resilience in HD Patient-Derived Neurons.Neuroscience bulletin · 2026Article
- Treatment with Neuronal-Induced Human Mesenchymal Stem Cells Improves Functional Recovery of Acute Spinal Cord Injury through Attenuating Astrogliosis and Neurotoxic Astrocyte Activation.Journal of Korean Neurosurgical Society · 2026Article
- Liver-derived complement component 3 promotes the susceptibility to stress-induced depression by impairing blood-brain barrier integrity.Molecular psychiatry · 2026Article
- Astrocytic LMP2 Coordinates NF-κB and TGF-β1/Smad3 Signaling to Drive Neuroinflammation after Cerebral Ischemia/Reperfusion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Innate immune signaling and functions in astrocytes.Nature immunology · 2026Review
- The complement C3-microglial axis in depression of Parkinson's disease: from mechanism to therapeutic intervention.EBioMedicine · 2026Article
- The complement system in Alzheimer's disease: evaluating biomarker potential in a complex neuroimmune context.Journal of neuroinflammation · 2026Review
- HDAC7 acts as an astrocytic mediator of Aβ pathology that directly engages IKK to drive astrocyte neurotoxicity and neurodegeneration in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Infiltrating Monocyte Fate Switch in Retinal Degeneration: From Early Pathology to Late Homeostasis.Research square · 2026Article
- Astrocyte-driven multicellular mechanisms of CNS repair and cerebroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Neuroprotection and immunomodulation after treatment with NeuroBoost and NeuroHeal following ventral root crush in mice.IBRO neuroscience reports · 2026Article
- The role of gut microbiota-mitochondria crosstalk in neurodegeneration: Underlying mechanisms and potential therapies.Neural regeneration research · 2026Article
- PTP1B in astrocytes drives pathogen-induced neurodegeneration.Journal of neuroinflammation · 2026Article
- Signaling cascades shape functional subpopulations of cortical astrocytes in male wild-type mice and APP/PS1dE9 Alzheimer's disease model.Nature communications · 2026Article
- Bindarit attenuates brain injury and neuroinflammation in status epilepticus by disrupting C3/C3aR signaling and modulating microglia-astrocyte interactions.Cell communication and signaling : CCS · 2026Article
350 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Abnormal NFκB activation has been implicated in Alzheimer's disease (AD). However, the signaling pathways governing NFκB regulation and function in the brain are poorly understood. We identify complement protein C3 as an astroglial target of NFκB and show that C3 release acts through neuronal C3aR to disrupt dendritic morphology and network function. Exposure to Aβ activates astroglial NFκB and C3 release, consistent with the high levels of C3 expression in brain tissue from AD patients and APP transgenic mice, where C3aR antagonist treatment rescues cognitive impairment. Therefore, dysregulation of neuron-glia interaction through NFκB/C3/C3aR signaling may contribute to synaptic dysfunction in AD, and C3aR antagonists may be therapeutically beneficial.
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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.