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Therapeutic Potential of Phosphodiesterase Inhibitors in Parasitic Diseases

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Phosphodiesterases as Drug Targets

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 204))

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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Acknowledgments

With many thanks to Simon Lockyer for proofreading the manuscript.

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Authors and Affiliations

  1. Otsuka Maryland Medicinal Laboratories Inc, 9900 Medical Center Drive, Rockville, MD, 20850, USA

    Yasmin Shakur & Junichi Kambayashi

  2. Institute of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, G12 8TA, UK

    Harry P. de Koning

  3. Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-260, USA

    Hengming Ke

  4. Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012, Bern, Switzerland

    Thomas Seebeck

Authors
  1. Yasmin Shakur
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  2. Harry P. de Koning
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  3. Hengming Ke
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  4. Junichi Kambayashi
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  5. Thomas Seebeck
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Corresponding author

Correspondence to Yasmin Shakur .

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Editors and Affiliations

  1. School of Medicine, Dept. Molecular Physiology & Biophysics, Vanderbilt University, Light Hall 702, Nashville, 37232-0615, Tennessee, USA

    Sharron H. Francis

  2. HSW 1656, Center for Reproductive Sciences, Parnassus Avenue 513, San Francisco, 94143-0556, California, USA

    Marco Conti

  3. Wolfson Building, University of Glasgow, Glasgow, G12 8QQ, United Kingdom

    Miles D. Houslay

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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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