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PLoS Negl Trop Dis. 2008 Sep 24;2(9):e298. doi: 10.1371/journal.pntd.0000298.

RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model.

Author information

1
Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biomedical Research, University of California San Francisco, San Francisco, California, USA. maha.abdulla@ucsf.edu

Abstract

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.

PMID:
18820745
PMCID:
PMC2553486
DOI:
10.1371/journal.pntd.0000298
[Indexed for MEDLINE]
Free PMC Article
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