Cyclic GMP-AMP Synthase (cGAS) Deletion Promotes Less Prominent Inflammatory Macrophages and Sepsis Severity in Catheter-Induced Infection and LPS Injection Models
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ABSTRACT:
PROVIDER: PRJNA1200068 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31762968_1.fastq.gz | Fastqsanger.gz | |||
| SRR31762968_2.fastq.gz | Fastqsanger.gz | |||
| SRR31762969_1.fastq.gz | Fastqsanger.gz | |||
| SRR31762969_2.fastq.gz | Fastqsanger.gz | |||
| SRR31762970_1.fastq.gz | Fastqsanger.gz |
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Project description:Here we report that activation of cyclic GMP-AMP synthase (cGAS) diminishes cognitive resilience by decreasing the neuronal transcriptional network of myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, in part mediated by cytosolic leakage of mitochondrial DNA. Genetic ablation of cGAS in tauopathy mice diminished microglial IFN-I response, preserved synapse integrity and plasticity, and protected against cognitive impairment without affecting the pathogenic tau load. cGAS ablation enhanced, while activation of IFN-I downregulated, neuronal MEF2C expression network linked with cognitive resilience in AD.
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