The proteasome as a drug target for treatment of parasitic diseases.

The proteasome is a proteolytically active molecular machine comprising many different protein subunits. It is essential for growth and survival in eukaryotic cells and has long been considered a drug target. Here, we summarize the biology of the proteasome, the early research relating to the development of specific proteasome inhibitors (PIs) for treatment of various cancers, and their translation and eventual evolution as exciting therapies for parasitic diseases. We also highlight the development and adaptation of technologies that have allowed for a deep understanding of the idiosyncrasies of individual parasite proteasomes, as well as the preclinical and clinical advancement of PIs with remarkable therapeutic indices.