FIGURE 5.

Vesicular trafficking impairment in PKAN leads to gliosis and neurodegeneration. Schematic cartoon illustrating our hypothesis of endosomal trafficking impairment in PKAN. (A) Normal condition, (B) altered dynamics in PKAN astrocytes. CoA deficiency in PKAN astrocytes leads to an impediment to normal physiological intracellular trafficking of the endosomal compartment. The aberrant endosomal behavior could be related to distorted biophysical properties of endosomes, such as membranes’ different lipid composition that modifies membranes fusion dynamics, but also to an unbefitting cytoskeletal milieu. The altered lipid composition by itself might also cause problems in the interactions between vesicles and normal cytoskeletal proteins.