Biology Reference
In-Depth Information
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 pharmaco-
logical 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.
Keywords Crystal structure
Kinetoplastid
Cyclic AMP
Cyclic nucleotide
phosphodiesterase
PDE inhibitor
RNA interference
Abbreviations
AC Adenylate cyclase
cAMP Cyclic 3
0
,5
0
adenosine monophosphate
cGMP Cyclic 3
0
,5
0
guanosine monophosphate
CL Cutaneous leishmaniasis
DAPI 4,6
0
-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
1
Introduction
Millions of people worldwide suffer from diseases caused by vector-borne proto-
zoan parasites. The main focus of this chapter is the causative agent of three of the
world's most important neglected diseases: African trypanosomiasis (sleeping
sickness), American trypanosomiasis (Chagas disease), and the leishmaniasis. In
particular, the current state of the art of the characterization and elucidation of the
functional role of the cyclic nucleotide phosphodiesterases (PDEs) in the life cycle
of these parasites and their potential as targets for new therapies are discussed.
1.1 Kinetoplastida: Life Cycle and Disease
Trypanosoma and Leishmania parasites are the causative agents of trypanosomiasis
and leishmaniasis, respectively; both are protozoan unicellular parasites belonging to
