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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience II

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE226381 | GEO | 2023/04/26

REPOSITORIES: GEO

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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience IV

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