This program is focused on the regulatory mechanisms involved in the altered peripheral/CNS innate immune response in neurological disorders, and in particular on the role of microglia and macrophages in both acute and chronic neuroinflammation observed in various CNS diseases. The program is led by Dr. Jasna Kriz from the Université Laval. Dr. Kriz has identified a novel target, SRSF3, as a key regulator of RNA splicing/transport and gene expression, which appears to play a central role analogous to a checkpoint of the innate immune system. As for T-cell checkpoints in oncology, removal of this off-switch in the innate immune response is predicted to have beneficial effects in human CNS disease, and particularly in diseases with an inflammatory component. The group is examining multiple modalities (anti-sense, siRNA, mAb) of SRSF3 targeting, and determining their usefulness in animal modeling of frontotemporal dementia and ALS.