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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Seebeck, Thomas Zoraghi, Roya |
| Description | Author Affiliation: Zoraghi R ( Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012 Bern, Switzerland.); |
| Abstract | Chemotherapy of human sleeping sickness, a fatal disease caused by the protozoan parasite Trypanosoma brucei, is in a dismal state, and the identification and characterization of new drug targets is an urgent prerequisite for an improvement of the dramatic situation in the field. Over the last several years, inhibitors of cyclic nucleotide-specific phosphodiesterases have proven to be highly successful drug candidates for an assortment of clinical conditions. Their potential as antiparasitic drugs has not been explored so far. This study reports the characterization of a cAMP-specific phosphodiesterase from T. brucei, TbPDE2C. This enzyme is a class I phosphodiesterase, and it is a member of a small enzyme family in T. brucei, TbPDE2. Inhibitors of this enzyme block the proliferation of bloodstream form trypanosomes in culture. RNA interference experiments demonstrated that the TbPDE2 family, and in particular TbPDE2C, are essential for maintaining intracellular cAMP concentrations within a physiological range. Bloodstream form trypanosomes are exquisitely sensitive to elevated concentrations of intracellular cAMP, and a disruption of TbPDE2C function quickly leads to the disruption of nuclear and cellular cell division, and to cell death. TbPDE2C might represent a novel drug target for the development of new and effective trypanocidal drugs. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 99 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2002-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Parasitemia Parasitology Phosphoric Diester Hydrolases Physiology Trypanosoma Brucei Brucei Enzymology Amino Acid Sequence Animals Catalysis Cyclic AMP Cyclic Nucleotide Phosphodiesterases, Type 2 Molecular Sequence Data Chemistry Genetics RNA, Double-Stranded Pharmacology RNA, Messenger Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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