Novel regulators of nucleic acid sensing drive neurotoxic interferon response in microglia

Mounting evidence shows that accumulation of cytoplasmic nucleic acids occurs as an early pathogenic marker of AD and that altering microglial responses to these disease-associated molecular patterns can abrogate symptom onset in murine models. We have discovered novel regulators of nucleic acid sensing and the interferon-responsive state using iPSC-derived microglial models and CRISPR screening technologies. These findings provide a foundation to support development of targeted therapies that inhibit IRM in vivo and restore protective functions of microglia.