ArticleCell death & disease2023
Cntnap4 partial deficiency exacerbates α-synuclein pathology through astrocyte-microglia C3-C3aR pathway.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
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- The mitophagy-inflammasome axis: a shared pathological hub in Alzheimer's and Parkinson's diseases.Translational neurodegeneration · 2026Review
- Astrocytes orchestrate neuroprotection and pathogenesis via bidirectional neuronal interactions in Parkinson's disease.Journal of physiology and biochemistry · 2026Review
- Complement dysregulation during the early phases of synucleinopathy.Acta neuropathologica · 2026Article
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Context-Dependent Regulation of Microglial Metabolic and Immune States via IL-3/CD123 Signaling: Implications for Glial Crosstalk and Cognitive Impairment.Molecular neurobiology · 2026Review
- The C3-C3aR axis drives rotenone-induced cognitive damage via synaptic engulfment, dark microglia and PANoptosis.Redox biology · 2026Article
- Microglia, Astrocytes, and Oligodendrocytes in Parkinson's Disease: Neuroinflammatory Crosstalk and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- RVG-targeted extracellular vesicles loaded with echinatin attenuate dopaminergic neurodegeneration via the IGF-2/PI3K/Akt pathway in Parkinson's disease mice.Journal of nanobiotechnology · 2026Article
- Analysis of the Immunoinflammatory Microenvironment Characteristics of Epilepsy Based on Single-Cell Transcriptomics.Journal of inflammation research · 2026Review
- Astrocytes in Parkinson's Disease: From Guardians to Accomplices.Clinical interventions in aging · 2026Review
- Molecular signaling pathways shaping astrocyte-microglia crosstalk in health and disease.Frontiers in molecular neuroscience · 2026Review
- Repetitive unidirectional spinal tactile stimulation engages microglial Bmal1 pathways to promote synaptic remodeling in the mPFC of adolescent VPA-exposed mice.Journal of neuroinflammation · 2025Article
- Microglial Extracellular Vesicles Mediate C1q Deposition at the Pre-Synapse and Promote Synaptic Pruning.Journal of extracellular vesicles · 2025Article
- Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts.Communications biology · 2025Article
- Histone H3 lysine 9 tri-methylation is associated with pterygium.BMC ophthalmology · 2025Article
- Microglia-Astrocyte Crosstalk in Post-Stroke Neuroinflammation: Mechanisms and Therapeutic Strategies.Current neuropharmacology · 2025Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is the most common progressive neurodegenerative movement disorder, which is characterized by dopaminergic (DA) neuron death and the aggregation of neurotoxic α-synuclein. Cntnap4, a risk gene of autism, has been implicated to participate in PD pathogenesis. Here we showed Cntnap4 lacking exacerbates α-synuclein pathology, nigrostriatal DA neuron degeneration and motor impairment, induced by injection of adeno-associated viral vector (AAV)-mediated human α-synuclein overexpression (AAV-hα-Syn). This scenario was further validated in A53T α-synuclein transgenic mice injected with AAV-Cntnap4 shRNA. Mechanistically, α-synuclein derived from damaged DA neuron stimulates astrocytes to release complement C3, activating microglial C3a receptor (C3aR), which in turn triggers microglia to secrete complement C1q and pro-inflammatory cytokines. Thus, the astrocyte-microglia crosstalk further drives DA neuron death and motor dysfunction in PD. Furthermore, we showed that in vivo depletion of microglia and microglial targeted delivery of a novel C3aR antagonist (SB290157) rescue the aggravated α-synuclein pathology resulting from Cntnap4 lacking. Together, our results indicate that Cntnap4 plays a key role in α-synuclein pathogenesis by regulating glial crosstalk and may be a potential target for PD treatment.
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