Fig. 2

Contributions of microglia and astrocytes in the pathogenesis of GRN-FTLD. In normal conditions progranulin, an anti-inflammatory molecule with many biological functions is produced in the CNS predominantly by microglia and to a lesser degree by astrocytes, endothelial cell and neurons. Its production is differentially regulated dependent on the cell type. GRN can be degraded by microglial MMP-12 to granulins with pro-inflammatory actions. This process is regulated by astrocytic SLP1 molecule. In GRN-FTLD the inflammatory milieu driven by genetic factors and proinflammatory mediators like granulins changes the morphology and function of glia cells. Microglia and astrocytes become activated with higher lysosomal and phagocytic activities that increases TDP-43 proteinopathy. Some molecules, genes and molecular pathways participating in the process are presented. Poly I:C polyinosinic:polycytidylic acid, SLP1 secretory leukocyte protease inhibitor