%0 Journal Article %T RNA Interference of Trypanosoma brucei Cathepsin B and L Affects Disease Progression in a Mouse Model %A Maha-Hamadien Abdulla %A Theresa O'Brien %A Zachary B. Mackey %A Mohamed Sajid %A Dennis J. Grab %A James H. McKerrow %J PLOS Neglected Tropical Diseases %D 2008 %I Public Library of Science (PLoS) %R 10.1371/journal.pntd.0000298 %X We investigated the roles played by the cysteine proteases cathepsin B and cathepsin L (brucipain) in the pathogenesis of Trypansoma brucei brucei in both an in vivo mouse model and an in vitro model of the blood¨Cbrain barrier. Doxycycline induction of RNAi targeting cathepsin B led to parasite clearance from the bloodstream and prevent a lethal infection in the mice. In contrast, all mice infected with T. brucei containing the uninduced Trypanosoma brucei cathepsin B (TbCatB) RNA construct died by day 13. Induction of RNAi against brucipain did not cure mice from infection; however, 50% of these mice survived 60 days longer than uninduced controls. The ability of T. b. brucei to cross an in vitro model of the human blood¨Cbrain barrier was also reduced by brucipain RNAi induction. Taken together, the data suggest that while TbCatB is the more likely target for the development of new chemotherapy, a possible role for brucipain is in facilitating parasite entry into the brain. %U http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000298