title: Plasmodial Hsp40s: New Avenues for Antimalarial Drug Discovery.
abstract: Malaria, an infectious disease caused by Plasmodium spp, is one of the world's most dangerous diseases, accounting for more than half a million deaths yearly. The long years of co-habitation between the parasite and its hosts (human and mosquito), is a testimony to the parasite's ability to escape the immune system and develop drug resistance mechanisms. Currently, an important search area for improved pharmacotherapy are molecular chaperones of the heat shock protein family, abundant in Plasmodium falciparum and contributing to its continuous survival and development. Thus far, small molecule inhibitor studies on P. falciparum Hsp70s and Hsp90s have indicated that they are promising antimalarial targets. However, not much attention has been given to Hsp40s as potential antimalarial drug targets. Hsp40s are known to function as chaperones by preventing protein aggregation, and as co-chaperones, by regulating the chaperone activities of Hsp70s to ensure proper protein folding. There are only a limited number of reviews on Hsp40s as drug targets, and the few reviews on plasmodial Hsp40s tend to focus largely on the intra-erythrocytic stage of the parasite life cycle. Therefore, this review will summarize what is known about Hsp40s throughout the malaria parasite life cycle, and critically evaluate their potential to serve as new avenues for antimalarial drug discovery.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife. Nigeria.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Daniyan
authors.affiliation: The Vice Chancellery, The University of Notre Dame Australia, Fremantle, Western Australia, Australia.|Biomedical Biotechnology Research Unit, Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Blatch
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D018832:Molecular Chaperones / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification; D017510:Protein Folding
chemical_list: D000962:Antimalarials; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones
keywords: Chaperones; Co-chaperones; Heat Shock Protein (Hsp); Malaria; PfHsp40s; Pharmacotherapy.; Plasmodium falciparum (Pf)