Exploring the role of Interleukin-6 (IL-6) in Rett syndrome: focus on astrocyte-neuron communication

Rett syndrome (RTT) is a neurodevelopmental disorder, mainly caused by mutations in the MECP2 gene, and for which a cure is still lacking. In the RTT brain, neurons are profoundly affected with respect to healthy neurons, showing a less complex morphology and few synapses, which represent the functional contact sites between neurons. The leading cause of these alterations can be ascribed, not only to the loss of function of MeCP2, but also to an abnormal functionality of another cell type that populates the brain, i.e. the astrocytes. While in physiological conditions astrocytes support neuronal maturation and formation of synapses, these abilities are partially lost in RTT. The mechanisms behind the defective communication between astrocytes and neurons are not completely known, although their identification could lead to uncover novel therapeutic targets.With the aim to discover the molecular mechanisms that in RTT astrocytes lead to the occurrence of neuronal defects, our research group has identified an abnormal secretion of Interleukin-6 (IL-6). Importantly, we observed increased levels of IL-6 in the brain of experimental models of RTT and literature evidence indicated its augmentation also in brain, plasma and saliva of RTT patients. In this project, we aim at understanding why IL-6 is overproduced by RTT astrocytes and testing whether blocking the action of this molecule might lead to neurological improvements in RTT animal models.