Split-ends is modulating lipid droplet content in adultDrosophilaglial cells and is protective against paraquat toxicity

Autor: Eloïse Dufourd, Victor Girard, Serge Nataf, Valérie Goubard, Nathalie Davoust, Laurent Pays, Laurent Seugnet, Matthieu Querenet, Bertrand Mollereau, David Cluet
Rok vydání: 2020
Předmět:
DOI: 10.1101/2020.05.20.101220
Popis: 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 ofspen,SPEN/SHARPbelongs to the set of astrocyte-expressed genes which mRNA levels are significantly different in thesubstantia nigraof PD patients as compared to controls. Interestingly, the retrieved list of differentially expressed genes was enriched in genes involved in lipid metabolism. In aDrosophilamodel of PD, we observed thatspenmutant flies were more sensitive to paraquat intoxication. Moreover, the glia-restricted knockdown ofspenled 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.
Databáze: OpenAIRE