Cyclic nucleotide signaling mechanisms in trypanosomes: possible targets for therapeutic agents.
Trypanosome infections cause several major human diseases, including sleeping sickness and Chagas disease, which affect millions of people in Africa and South America, respectively. Although adenosine 3',5'-monophosphate (cAMP) signaling and regulation have been widely studied in mammalian systems, and these pathways provide targets for the treatment of numerous pathologies, a molecular understanding of cAMP signaling in trypanosomes remains incomplete. Recent studies in these parasites, however, have revealed diverse families of adenylyl cyclase and phosphodiesterase that regulate cAMP concentrations. Importantly, these enzymes differ pharmacologically and biochemically from their mammalian counterparts. In this review, we discuss recent developments, emerging ideas, and gaps in knowledge in this area of research, highlighting aspects of enzymes in the cAMP signaling pathway that may be good targets for antitrypanosomal drug therapy.
Laxman
Sunil
S
Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98105, USA. sunil.laxman@utsouthwestern.edu
Beavo
Joseph A
JA
D000262:Adenylyl Cyclases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010727:Phosphoric Diester Hydrolases / Q000145:classification / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D015290:Second Messenger Systems / Q000502:physiology*; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use; D014345:Trypanosoma / Q000187:drug effects* / Q000378:metabolism* / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology