Figure 3.

Schematic representation of the possible mechanism of action of oxidized/deamidated ceruloplasmin (Cp-ox/de) on choroid plexus epithelial cells. In healthy conditions, the blood-cerebrospinal fluid barrier (BCSFB) is intact and ceruloplasmin (Cp) is retained in the cerebrospinal fluid (CSF), exerting ferroxidase activity. Under pathological conditions, Cp is modified by the pro-oxidant environment that promotes Asparagine-Glycine-Arginine (NGR) motifs deamidation and loss of copper ions, inhibiting Cp ferroxidase activity. The oxidative environment also induces the leakage of the BCSFB, and allows Cp-ox/de to cross the choroid plexus epithelial monolayer. Once in the basal side, Cp-ox/de binds integrins via isoAspartate-Glycine-Arginine (isoDGR) motif, transducing an intracellular signal that might affect integrin-mediated interaction with the extracellular matrix (ECM), modify secretome components profile, and induce cell proliferation inhibition.