Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity.

ABSTRACT: Ceramides are lipids that play vital roles in complex lipid synthesis, membrane function, and cell signaling. Disrupted ceramide homeostasis is implicated in cell-death and several neurologic diseases. Ceramides are often analyzed in tissue, but this approach fails to resolve cell-type differences in ceramide homeostasis that are likely essential to understanding cell and non-cell autonomous contributions to neurodegeneration. We show that human iPSC-derived neurons and glia differ in their rate of ceramide synthesis, ceramide isoform composition, and responses to altered ceramide levels. RNA-sequencing of cells treated to increase or decrease ceramides revealed connections to inflammation, ER stress, and apoptosis. Moreover, introducing labeled sphinganine showed that glia readily synthes

SUBMITTER: McInnis JJ 

PROVIDER: S-EPMC11608238 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature