Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils

Leishmania, the causative agent of leishmaniasis, is an intracellular pathogen that thrives in the insect gut and mammalian macrophages to complete its life cycle. Apart from temperature difference (26 to 37°C), it encounters several harsh conditions, including oxidative stress, inflammatory reactions, and low pH. Heat shock proteins (HSPs) play essential roles in cell survival by strategically reprogramming cellular processes and signaling pathways. HSPs assist cells in multiple functions, including differentiation, adaptation, virulence, and persistence in the host cell. Due to cyclical epidemiological patterns, limited chemotherapeutic options, drug resistance, and the absence of a vaccine, control of leishmaniasis remains a far-fetched dream. The essential roles of HSPs in parasitic differentiation and virulence and increased expression in drug-resistant strains highlight their importance in combating the disease. In this review, we highlighted the diverse physiological importance of HSPs present in Leishmania, emphasizing their significance in disease pathogenesis. Subsequently, we assessed the potential of HSPs as a chemotherapeutic target and underlined the challenges associated with it. Furthermore, we have summarized a few ongoing drug discovery initiatives that need to be explored further to develop clinically successful chemotherapeutic agents in the future.