Abstract
Protozoan parasites of the order kinetoplastida are the causative agents of three of the world’s most important neglected human diseases: African trypanosomiasis, American trypanosomiasis, and leishmaniasis. Current therapies are limited, with some treatments having serious and sometimes lethal side effects. The growing number of cases that are refractory to treatment is also of concern. With few new drugs in development, there is an unmet medical need for new, more effective, and safer medications. Recent studies employing genetic and pharmacological techniques have begun to shed light on the role of the cyclic nucleotide phosphodiesterases in the life cycle of these pathogens and suggest that these important regulators of cyclic nucleotide signaling may be promising new targets for the treatment of parasitic diseases.
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Abbreviations
- AC:
-
Adenylate cyclase
- cAMP:
-
Cyclic 3′,5′ adenosine monophosphate
- cGMP:
-
Cyclic 3′,5′ guanosine monophosphate
- CL:
-
Cutaneous leishmaniasis
- DAPI:
-
4,6′-diamidino-2-phenylindole
- EPAC:
-
Exchange protein activated by cAMP
- HAT:
-
Human African trypanosomiasis
- IBMX:
-
Isobutyl-1-methylxanthine
- MCL:
-
Mucocutaneous leishmaniasis
- PDE:
-
Cyclic nucleotide phosphodiesterase
- PKA:
-
Protein kinase A
- RNAi:
-
RNA interference
- SIF:
-
Stumpy inducing factor
- VL:
-
Visceral leishmaniasis
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With many thanks to Simon Lockyer for proofreading the manuscript.
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Shakur, Y., de Koning, H.P., Ke, H., Kambayashi, J., Seebeck, T. (2011). Therapeutic Potential of Phosphodiesterase Inhibitors in Parasitic Diseases. In: Francis, S., Conti, M., Houslay, M. (eds) Phosphodiesterases as Drug Targets. Handbook of Experimental Pharmacology, vol 204. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17969-3_20
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