Fig. 8

Diagram showing the effects of FXN deficiency in human astrocytes and the therapeutic effect of SAG. FXN depletion in HAs induces a series of negative effects on the cells including (1) changes in mitochondrial number, dynamics and function, (2) increased mitochondrial elimination through mitophagy, (3) secretion of the reactivity marker C3, (4) reduced production of neurotrophic factors and (5) higher release o of pro-inflammatory cytokines. In addition, FXN deficiency altered HA function, having a negative impact in neuronal status, i.e., reducing neuronal survival, branching and synapse formation (6). Most of these changes, including the indirect neurotoxic effects induced by the lack of FXN in HAs, were inhibited by a chronic treatment with SAG, a SHH pathway agonist (7). FXN frataxin, ROS reactive oxygen species, C3 complement component C3, SAG smoothened agonist