cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition of Plasmodium falciparum Blood Stages

We review the role of signaling pathways in regulation key processes merozoite egress and red blood cell invasion by Plasmodium falciparum and, particular, importance second messengers, cAMP Ca 2+ , cyclic nucleotide dependent kinases. cAMP-dependent protein kinase (PKA) is comprised cAMP-binding regulatory, catalytic subunits. The less well conserved pockets should make analogs attractive drug leads, but this approach compromised poor membrane permeability nucleotides. discuss how nature ATP-binding makes ATP inherently prone to off-target effects genetic manipulation can be useful research tools examine this. suggest that targeting PKA interaction partners as substrates, or developing inhibitors based on sites phosphorylation may provide viable alternative approaches for development anti-malarial drugs. Proximity a substrate necessary phosphorylation, P. genome encodes few recognizable A-kinase anchor proteins (AKAPs), suggesting PKA-regulatory subunit myristylation association determining preference. also Pf14-3-3 assembles phosphorylation-dependent complex includes calcium 1 (CDPK1) critical invasion, target block parasite growth. compare altered levels intracellular egressed merozoites identify potential substrates. Finally, host have supporting development, we its at other stages life cycle, apicomplexan infections. Throughout our propose possible new directions therapeutic exploitation cAMP-PKA-signaling malaria diseases caused parasites.