ArticleNPJ Parkinson's disease2025
Complement C4 exacerbates astrocyte-mediated neuroinflammation and promotes α-synuclein pathology in Parkinson's disease.
Article in NPJ Parkinson's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The trial behind it
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Who cites it
10 citing papers in PubMed.
- Astrocyte reactivity by alcohol dependence in the central amygdala.Brain, behavior, and immunity · 2026Article
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Selective Neuronal Vulnerability to Alpha-Synuclein Pathology in Parkinson's Disease: A Critical Review of Mechanistic Rationale and Biomarker Stratification.Medical sciences (Basel, Switzerland) · 2026Review
- Complement dysregulation during the early phases of synucleinopathy.Acta neuropathologica · 2026Article
- The complement C3-microglial axis in depression of Parkinson's disease: from mechanism to therapeutic intervention.EBioMedicine · 2026Article
- Preclinical serum alterations and tissue changes in protein and gene expression of early cerebrospinal fluid-validated biomarkers in scrapie.Veterinary research · 2026Article
- Astrocyte Reactivity by Alcohol Dependence in the Central Amygdala.bioRxiv : the preprint server for biology · 2026Article
- Microglia, Astrocytes, and Oligodendrocytes in Parkinson's Disease: Neuroinflammatory Crosstalk and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- Complement pathway dysregulation and astrocyte alterations in Down syndrome: evidence from postmortem brain tissue and iPSC-derived astrocytes.Acta neuropathologica communications · 2025Article
- Astrocytic and microglial cell functions in neuroinflammatory diseases and their animal models.Frontiers in cellular neuroscience · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Complement C4, implicated in neuroinflammation and synaptic dysfunction, plays a poorly defined role in Parkinson's disease (PD). Here, we demonstrate elevated C4 levels in PD patient plasma and the substantia nigra of α-synuclein preformed fibril (α-syn PFF)-injected mice, correlating with disease severity. α-syn PFF treatment induces complement C4 expression, particularly in neurons, with astrocytes further enhancing this response. Complement C4 was found to amplify astrocytic inflammatory responses, leading to increased neuronal apoptosis and synaptic damage. Additionally, conditioned media from astrocytes treated with α-syn PFF and complement C4 accelerated α-syn aggregation and synaptic loss in cultured neurons. In vivo, complement C4 exacerbated motor dysfunction, dopaminergic neuronal loss, and α-syn pathology in α-syn PFF-injected mice. These findings reveal that complement C4 significantly contributes to the neuroinflammatory environment and α-syn pathology in PD, highlighting its potential as a therapeutic target for mitigating neurodegeneration in this disorder.
Identifiers
What Socratic 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 Socratic graph.