Fig. 9From: Lipid microdomain modification sustains neuronal viability in models of Alzheimer’s diseaseGCS inhibition increases neuronal viability in AD and increases the levels of functional IR on the neuronal cell surface. The proposed mechanism suggests that GCS-derived gangliosides facilitate ADDL-mediated internalization of surface IR via caveolin-1-containing caveolae. Low levels of caveolin-1 in GCS-deficient neurons lead to increased levels of IR at the neuronal surface. IR sensitivity and signaling are maintained in GCS-deficient neurons despite exposure to ADDLs. This contributes to the increased neuronal viability observed in AD models in vivo, where neurons harbor a genetic GCS deletion or in vitro, when they are treated with the specific GCS inhibitor GENZBack to article page