Fig. 9.

Schematic representation of GCase inhibitions on microglia and neuron communication. Microglia, through actin-dependent structures, directly contact neurons and induce a detoxification response by increasing the NFE2L2 signaling pathway. Inhibition of GCase activity by CBE treatment produces a morpho-functional change in microglia which acquire a morphology and gene expression pattern reminiscent of Gaucher’s cells. This phenotype shift hampers the neuroprotective microglia-neuron communication thus inducing a phenotype in dopaminergic neurons characterized by increased susceptibility to oxidative stress or toxic insults