JCI table of contents: September 21, 2006


View the PDF of this article at: https://www.the-jci.org/article.php?id=27209

PARASITOLOGY: Brucipain gives parasite open access to the brain

It is estimated that 40,000 people in sub-Saharan Africa die every year of sleeping sickness. Sleeping sickness occurs when individuals become infected with one of two parasites, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. The final stages of the disease are characterized by neurological defects and occur when the parasite leaves the bloodstream and enters the brain. The mechanisms by which the parasites invade the brain have not been well defined. Now, in a study using human cells in culture, which appears online on September 21 in advance of publication in the October print issue of the Journal of Clinical Investigation, researchers from Johns Hopkins School of Medicine, have shown that the T. b. gambiense protein brucipain, which can destroy other proteins, enables the parasite to get past the cells that act as a barrier between the blood and the brain.

Dennis Grab and colleagues showed that inhibitors of brucipain prevented T. b. gambiense getting past the cells that act as a barrier to entry into the brain. Conversely, a mixture of the soluble factors produced by T. b. gambiense, which includes brucipain, helped a related parasite T. b. brucei that normally cannot get past these barrier cells cross the barrier. Further analysis showed that brucipain activates the cells that form the barrier to the brain, but exactly how this provides T. b. gambiense access to the brain remains to be determined.

TITLE: Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease

AUTHOR CONTACT: Dennis J. Grab Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Phone: (410) 614-3917; Fax: (410) 614-1

Contact: Karen Honey
Journal of Clinical Investigation

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