FIGURE 8.

Schematic model of astrocyte derived EV‐IL‐1β promoted neuronal APP amyloidogenic processing. Astrocytes stimulated with IL‐1β (astrocyte derived EV‐IL‐1β, ADEV‐IL‐1β) shed extracellular vesicles that are enriched with CK1. Astrocyte derived EV‐IL‐1β is delivered to neurons where the CK1 originating from astrocytes binds with neuronal APC and GSK to inhibit the β‐catenin degradation complex. Stabilized β‐catenin translocates to the nucleus and binds the Hnrnpc gene promoter regions ‐2.7 and ‐0.3 kb to enhance hnRNP C expression. This binding is fundamentally different from β‐catenin binding induced by classical Wnt signaling. The hnRNP C protein dislocates the translational repressor FMRP and binds to APP mRNA promoting the translation of APP mRNA. APP protein accumulates in membrane microdomains with BACE1 to promote the amyloidogenic processing of APP into Aβ peptides