Fig. 6
From: Induction of the type I interferon response in neurological forms of Gaucher disease
Proposed mechanism by which type I IFN is activated in nGD. Left Induction of the IFN response in neurons upon GlcCer accumulation. Elevated levels of GlcCer are sensed directly or indirectly by a PRR resulting in activation of the antiviral response and production of IFNα and IFNβ. IFN is secreted from neurons and engages IFNAR in neighboring cells, i.e., microglia. Right Upon engagement, IFNAR activates phosphorylation, dimerization, and nuclear translocation of STAT proteins, which subsequently induce the expression of ISGs, among them MLKL, which forms the necrosome complex together with phosphorylated RIP3