TY - CHAP
T1 - RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model
AU - Abdulla, Maha Hamadien
AU - O'Brien, Theresa
AU - Mackey, Zachary B.
AU - Sajid, Mohamed
AU - Grab, Dennis J.
AU - McKerrow, James H.
PY - 2008/8
Y1 - 2008/8
N2 - 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-brain 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-brain 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.
AB - 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-brain 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-brain 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.
UR - http://www.scopus.com/inward/record.url?scp=56149088299&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56149088299&partnerID=8YFLogxK
U2 - 10.1371/journal.pntd.0000298
DO - 10.1371/journal.pntd.0000298
M3 - Chapter
C2 - 18820745
AN - SCOPUS:56149088299
VL - 2
BT - PLoS Neglected Tropical Diseases
ER -