Figure 3.

Proteolytic pathways involved in IAPP degradation. (1) ALS is involved in degradation of misfolded IAPP localized outside nucleus. (2) UPS regulates degradation of misfolded IAPP localized in cytosol and nucleus. Diabetogenic stresses downregulate both (1) and (2). UCHL1 probably regulates both (1–3) hIAPP aggregate inhibits both (1) and (2). (4) IDE degrades cytosolic hIAPP aggregates. (5) MMP-9 and neprilysin degrade secreted form of hIAPP and/or inhibits fibril formation, thereby preventing its aggregation on the beta-cell.