FIG. 7.

Tau and the proteasome. There are two pathways for degradation of phosphorylated tau: ATP-independent degradation by the 20S proteasome, or ubiquitinylation by the E3 CHIP ligase, and subsequent degradation by the ATP-dependent 26S Proteasome. Although a minimal amount of selective Tau phosphorylation activates degradation by the 26S Proteasome, excessive and unregulated Tau phosphorylation (hyperphosphorylation) inhibits the Proteasome, exacerbating the pathology and cellular damage. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars