title: Typical 2-Cys peroxiredoxins in human parasites: Several physiological roles for a potential chemotherapy target.
abstract: Peroxiredoxins (Prxs) are ubiquitary proteins able to play multiple physiological roles, that include thiol-dependent peroxidase, chaperone holdase, sensor of H2O2, regulator of H2O2-dependent signal cascades, and modulator of the immune response. Prxs have been found in a great number of human pathogens, both eukaryotes and prokaryotes. Gene knock-out studies demonstrated that Prxs are essential for the survival and virulence of at least some of the pathogens tested, making these proteins potential drug targets. However, the multiplicity of roles played by Prxs constitutes an unexpected obstacle to drug development. Indeed, selective inhibitors of some of the functions of Prxs are known (namely of the peroxidase and holdase functions) and are here reported. However, it is often unclear which function is the most relevant in each pathogen, hence which one is most desirable to inhibit. Indeed there are evidences that the main physiological role of Prxs may not be the same in different parasites. We here review which functions of Prxs have been demonstrated to be relevant in different human parasites, finding that the peroxidase and chaperone activities figure prominently, whereas other known functions of Prxs have rarely, if ever, been observed in parasites, or have largely escaped detection thus far.
authors.affiliation: Department of Health, Life and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelucci
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Rome, Italy.
authors.forename: Adriana Erica
authors.initials: AE
authors.lastname: Miele
authors.affiliation: Department of Health, Life and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ardini
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Boumis
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Rome, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Saccoccia
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Rome, Italy. Electronic address: andrea.bellelli@uniroma1.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bellelli
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D015870:Gene Expression; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010961:Plasmodium / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D011528:Protozoan Infections / Q000188:drug therapy* / Q000469:parasitology; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012547:Schistosoma / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014122:Toxoplasma / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014345:Trypanosoma / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D018832:Molecular Chaperones; D015800:Protozoan Proteins; D010544:Peroxidases; D054464:Peroxiredoxins
keywords: Chaperone holdase; Leishmaniasis; Malaria; Peroxiredoxin; Schistosomiasis; Thioredoxin-dependent peroxidase; Toxoplasmosis; Trypanosomiasis