Fig. 8.

Schematic illustration of the intracellular responses affected by monomeric tau endocytosis. Monomeric tau is rapidly internalized by both neuronal and glial cells, mediated by the actin-dependent macropinocytosis pathway. In addition, an important role of HSPG has been demonstrated in regulating inflammatory gene expression, including IL-6 and IL-1β, partially via ERK1/2 activation following tau uptake. LRP1 modulates IL-6 responses to tau endocytosis, and this interaction is HSPG-dependent but not ERK-dependent. Solid arrows represent the pathways that have been demonstrated in this study. Dashed arrows represent the pathways speculated to be responsible for subsequent cellular responses based on other relevant publications, as described in the “Discussion” section