title: Threonine peptidases as drug targets against malaria.
abstract: BACKGROUND
  Malaria is caused by the intracellular parasite Plasmodium falciparum. Although numerous therapies are available to fight the disease, the number of pharmacophores is small, and constant development of novel therapies, especially with new targets, is desirable to fight developing resistance against presently prescribed drugs.
  
  
  METHODS
  This review discusses research on plasmodial threonine peptidases along with recent advances in proteasome inhibitor development.
  
  
  CONCLUSIONS
  While PfHslV is an attractive drug target in malaria, more investigation is required to clarify its functional role in the parasite. More efforts should also be invested in assessing the plasmodial proteasome as a drug target. The few papers investigating the effect of proteasome inhibitors on different stages of the life cycle point towards important roles not only during asexual, but also in hepatic and sexual stages, in humans and the mosquito. If this holds true, this is a key argument to further develop proteasome inhibitors for use against malaria.
authors.affiliation: University of Tübingen, Institute of Tropical Medicine, Wilhelmstr. 27, 72074 Tübingen, Germany.
authors.forename: Serena
authors.initials: S
authors.lastname: Tschan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009033:Culicidae; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D011480:Protease Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D061988:Proteasome Inhibitors; D013912:Threonine / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D013912:Threonine; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex