Spen modulates lipid droplet content in adult Drosophila glial cells and protects against paraquat toxicity.
Sci Rep, 10(1):20023.
Glial cells are early sensors of neuronal injury and can store lipids in lipiddroplets under oxidative stress conditions. Here, we investigated the functions ofthe RNA-binding protein, SPEN/SHARP, in the context of Parkinson's disease (PD).Using a data-mining approach, we found that SPEN/SHARP is one of manyastrocyte-expressed genes that are significantly differentially expressed in thesubstantia nigra of PD patients compared with control subjects. Interestingly, thedifferentially expressed genes are enriched in lipid metabolism-associated genes. Ina Drosophila model of PD, we observed that flies carrying a loss-of-function alleleof the ortholog split-ends (spen) or with glial cell-specific, but notneuronal-specific, spen knockdown were more sensitive to paraquat intoxication,indicating a protective role for Spen in glial cells. We also found that Spen is apositive regulator of Notch signaling in adult Drosophila glial cells. Moreover,Spen was required to limit abnormal accumulation of lipid droplets in glial cells ina manner independent of its regulation of Notch signaling. Taken together, ourresults demonstrate that Spen regulates lipid metabolism and storage in glial cellsand contributes to glial cell-mediated neuroprotection.
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