Peptidases in autophagy are therapeutic targets for Leishmaniasis

Differentiation of Leishmania life forms is crucial for progression and preadaptation of the parasite to the environmental conditions existing in its hosts. Autophagy is a catabolic degradation process that utilizes cytosolic ATG4s and lysosomal cathepsins to affect protein turnover and remodeling, which are crucial for parasite development, differentiation, and virulence. In this chapter, published data on the physiological roles of the cysteine peptidases involved in autophagy and virulence in Leishmania spp. that establishes them as therapeutic targets will be reviewed. Potential lead compounds that can modulate the activities of the cysteine peptidases for therapeutic advantage, the challenges involved, and the opportunities they provide for drug development to control leishmaniasis will be discussed.