FIG. 6.

Aβ and the proteasome. Aβ plays a central role in Alzheimer's disease, and it has a well-established relationship with the proteasome. BACE-1, an enzyme that was fundamental in forming Aβ, is ubiquitinylated by the E3 CHIP ligase, for degradation by the ATP-dependent 26S proteasome, thus decreasing the amount of Aβ peptide generated. The 20S proteasome is directly inhibited by Aβ, thus blocking the effective removal of oxidized proteins. In response to the increased cellular damage caused by oxidative stress, the cell increases de novo synthesis of the IP. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars