ArticleNature communications2024
C5aR1 antagonism suppresses inflammatory glial responses and alters cellular signaling in an Alzheimer's disease mouse model.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed.
- Early amyloid pathology in mice synergistically worsens post-sepsis behavioral impairment and microglial synaptic phagocytosis.Brain, behavior, & immunity - health · 2026Article
- Article
- Complement Activation by Post-Translationally Modified Proteins: Links to Chronic Inflammation and Autoimmunity.Immunological reviews · 2026Review
- Targeting Microglial C5aR1 with PMX205 Attenuates Neuroinflammation and Improves Neurological Recovery After Intracerebral Hemorrhage.Neurochemical research · 2026Article
- Complement dysregulation during the early phases of synucleinopathy.Acta neuropathologica · 2026Article
- Reshaping the immune landscape: next-generation microglia-targeted therapies for Alzheimer's disease.Biological research · 2026Review
- The complement system in Alzheimer's disease: evaluating biomarker potential in a complex neuroimmune context.Journal of neuroinflammation · 2026Review
- Microporous annealed particle scaffolds avoid foreign body response by down regulating complement-fibroblast-macrophage signaling loop.bioRxiv : the preprint server for biology · 2026Article
- Targeting microglial C1q alleviates blood-brain barrier disruption in the thalamus after cortical infarction.Journal of neuroinflammation · 2026Article
- CRISPR-Cas9 and next-generation gene editing strategies for therapeutic intervention of neurodegenerative pathways in Alzheimer's disease: a state-of-the-art review.Acta neurologica Belgica · 2026Review
- Alzheimer's Disease: From Pathogenesis to Emerging Therapeutic Targets.Journal of clinical medicine · 2026Review
- Toxoplasma gondii drives myeloid immune cell recruitment to amyloid plaques in Alzheimer's model mice.Journal of neuroinflammation · 2026Article
- C5aR1 Inhibition Alleviates Cranial Radiation-Induced Cognitive Decline.Cancer research · 2026Article
- The complement system in Alzheimer's disease: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
- The inner fire: the shifting paradigm of complement system in aging.Frontiers in immunology · 2026Review
- Remodeling of the brain immune microenvironment in Alzheimer's disease: interactions among microglia, astrocytes, complement, and the neurovascular unit.Frontiers in immunology · 2026Review
- Microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and emerging therapeutic targets.Frontiers in cellular neuroscience · 2026Review
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Regulatory T cells promote microglia-mediated synapse engulfment and functional recovery via the OPN-CD74 axis after spinal cord injury in mice.Journal of neuroinflammation · 2025Article
- Complement pathway dysregulation and astrocyte alterations in Down syndrome: evidence from postmortem brain tissue and iPSC-derived astrocytes.Acta neuropathologica communications · 2025Article
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9 authors.
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Abstract
Alzheimer's disease (AD) is the leading cause of dementia in older adults, and the need for effective, sustainable therapeutic targets is imperative. The complement pathway has been proposed as a therapeutic target. C5aR1 inhibition reduces plaque load, gliosis, and memory deficits in animal models, however, the cellular bases underlying this neuroprotection were unclear. Here, we show that the C5aR1 antagonist PMX205 improves outcomes in the Arctic48 mouse model of AD. A combination of single cell and single nucleus RNA-seq analysis of hippocampi derived from males and females identified neurotoxic disease-associated microglia clusters in Arctic mice that are C5aR1-dependent, while microglial genes associated with synapse organization and transmission and learning were overrepresented in PMX205-treated mice. PMX205 also reduced neurotoxic astrocyte gene expression, but clusters associated with protective responses to injury were unchanged. C5aR1 inhibition promoted mRNA-predicted signaling pathways between brain cell types associated with cell growth and repair, while suppressing inflammatory pathways. Finally, although hippocampal plaque load was unaffected, PMX205 prevented deficits in short-term memory in female Arctic mice. In conclusion, C5aR1 inhibition prevents cognitive loss, limits detrimental glial polarization while permitting neuroprotective responses, as well as leaving most protective functions of complement intact, making C5aR1 antagonism an attractive therapeutic strategy for AD.
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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.