Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366768267> ?p ?o ?g. }
- W4366768267 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." @default.
- W4366768267 created "2023-04-25" @default.
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- W4366768267 date "2023-04-22" @default.
- W4366768267 modified "2023-10-14" @default.
- W4366768267 title "Cntnap4 partial deficiency exacerbates α-synuclein pathology through astrocyte–microglia C3-C3aR pathway" @default.
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- W4366768267 doi "https://doi.org/10.1038/s41419-023-05807-y" @default.
- W4366768267 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37087484" @default.
- W4366768267 hasPublicationYear "2023" @default.
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