Figure 4.

The degradation of tau proteins. Tau can be targeted by both the UPS and macroautophagy, depending on the nature of post-translational modifications that influence folding and solubility. In general, soluble monomeric tau proteins are recognized by molecular chaperones and Ub ligases, such as CHIP, leading to the formation of ubiquitinated tau proteins. It remains unclear as to what extent ubiquitinated tau proteins are actually degraded by the proteasome. Alternatively, the same substrates can be directly delivered to the 20S proteasome without ubiquitination. Some tau proteins prone to rapid aggregation, such as hyperphosphorylated species, can be delivered to p62 and, subsequently, autophagosomes for lysosomal degradation. Modified from Chesser et al.²²⁷