Can the Plasmodium falciparum Nedd8 pathway provide new targets for malaria control?

点击翻译按钮获取中文摘要

Ubiquitin and Nedd8 are involved in fundamental cellular processes and are essential to all eukaryotes. As such, enzymes mediating their dynamic attachment and removal from substrates present attractive targets for therapeutic intervention for both chronic and communicable diseases. Despite being evolutionarily conserved, differences in how these pathways are controlled in higher and lower eukaryotes do exist and could potentially be exploited to generate pathogen-specific inhibitors. It is, therefore, necessary to understand the cell biological mechanisms behind how these pathways are regulated. We have evidence to support that removal of Nedd8 from target proteins in the malaria parasite, Plasmodium falciparum, is mediated by different enzymes than those of the human host. We now aim to characterize enzymes involved in Nedd8 attachment. We also aim to assess whether these enzymes are essential to P. falciparum survival and if they can be selectively disrupted in the parasite through peptide inhibitors. Overall, we hope to gain a better understanding of how the Nedd8 pathway has evolved across eukaryotes and identify patterns to predict its function in other parasites more widely.