You are here

GlcSph in GD-iPSC-derived Neurons Deregulates Lysosomes

Using induced pluripotent stem cell (iPSC)‐derived neurons from patients with neuronopathic Gaucher disease (GD), a new study from the lab of Ricardo A. Feldman (University of Maryland, Baltimore, Maryland, USA) describes a pathogenic mechanism by which glucosylsphingosine (GlcSph), a neurotoxic lipid that accumulates in GD brains, deregulates the lysosomal compartment. In their STEM CELLS Translational Medicine article, Srikanth et al. found that elevated GlcSph activated the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) to interfere with normal lysosomal biogenesis and autophagy. However, inhibition of mTOR kinase, glucosylceramide synthase, and acid ceramidase, the enzyme responsible for the generation of GlcSph, reversed said abnormalities.