Split-ends is modulating lipid droplet content in adult Drosophila glial cells and is protective against paraquat toxicity.

Glial cells are early sensors of neuronal injury and are able to store lipids in lipid droplets under oxidative stress conditions. Here, we investigated the glial functions of Spen in the context of Parkinson's disease (PD). Using a data mining approach, we first found that the human ortholog of spen, SPEN/SHARP belongs to the set of astrocyte-expressed genes which mRNA levels are significantly different in the substantia nigra of PD patients as compared to controls. Interestingly, the retrieved list of differentially expressed genes was enriched in genes involved in lipid metabolism. In a Drosophila model of PD, we observed that spen mutant flies were more sensitive to paraquat intoxication. Moreover, the glia-restricted knockdown of spen led to the expansion and the accumulation of lipid droplets as well as the inhibition of Notch pathway. Taken together our results show that Spen regulates lipid metabolism and storage in glial cells and by these means contribute to glia-mediated functions in the context of neurodegeneration.