Fig. 5

Schematic diagram illustrating proteasome activities, Aβ degradation, and oxidative stress which causes the Aβ degrading proteases to malfunction. (1) Aβ-degrading proteases (IDE and NEP) degrade monomeric and oligomeric forms of Aβ through Aβ degradation [78]. (2) Oxidative stress modifies the Aβ-degrading proteases via HNE, a product of lipid peroxidation. (3) The HNE modification of proteins, caused by oxidative stress, impairs the activities of Aβ-degrading proteases. (4) Proteasome degrades the HNE-modified proteins via the ubiquitin–proteasome and lysosomal pathways. (5) However, Aβ oligomers can inhibit all of the proteasome activities by inhibiting the 19S proteasome, resulting in the impairment of proteasome activity