The proteasome as a target for protozoan parasites

Abstract

Introduction: The proteasome is a multi-subunit enzyme complex responsible for the turnover of short-lived, abnormal or damaged proteins in eukaryotic cells. As organisms that undergo rapid growth and cell division, protozoan parasites exist on the knife-edge of proteotoxic catastrophe and thus rely heavily on their protein quality control machinery for survival. Because of this, the proteasome has recently emerged as a desirable drug target. Area covered: This review focuses on efforts to identify protozoan parasite-specific proteasome inhibitors using substrate profiling, library screening, and in vitro evolution of resistance approaches to inform medicinal chemistry. Targeting the parasit..