Fig. 1
From: Lipid microdomain modification sustains neuronal viability in models of Alzheimer’s disease
GCS inhibition by GENZ-123346 leads to increased viability of hippocampal mHippoE-14 neurons exposed to Aβ1-42-derived diffusible ligands (ADDLs). a General ganglioside biosynthesis and the neuronal a-series gangliosides expressed in mHippoE-14 cells (outlined). Pharmacological inhibition of the key enzyme involved in ganglioside biosynthesis, glucosylceramide synthase (GCS) by the ceramide analogue Genz123346 (GENZ) abates ganglioside biosynthesis. b Thin layer chromatography (TLC) shows that a concentration of 5 μM GENZ (7 days) efficiently inhibits ganglioside biosynthesis in mHippoE-14 cells. c An MTT assay confirms the toxicity of the ADDLs (white bar). However, GENZ treatment increases neuronal viability upon ADDL stress (grey bar; n = 5-12 replicates). d Western blot shows that total insulin receptor (IR) levels are increased in GENZ-treated mHippoE-14 cells (n = 4). Unpaired two-tailed student’s t-test (p ≤ 0.001 is marked with (***)); 5 μM ADDLs, 24 h; 100nM insulin, 10 min. Means ± SEM