Hsp70s and J Proteins of Plasmodium Parasites Infecting Rodents and Primates: Structure, Function, Clinical Relevance, and Drug Targets

Author(s): James M. Njunge, Michael H. Ludewig, Aileen Boshoff, Eva-Rachele Pesce, Gregory L. Blatch

Journal Name: Current Pharmaceutical Design

Volume 19 , Issue 3 , 2013


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Abstract:

Human malaria is an economically important disease caused by single-celled parasites of the Plasmodium genus whose biology displays great evolutionary adaptation to both its mammalian host and transmitting vectors. While the parasite has multiple life cycle stages, it is in the blood stage where clinical symptoms of the disease are manifested. Following erythrocyte entry, the parasite resides in the parasitophorous vacuole and actively transports its own proteins to the erythrocyte cytosol. This host-parasite “cross-talk” results in tremendous modifications of the infected erythrocyte imparting properties that allow it to adhere to the endothelium preventing splenic clearance. The Hsp70-J protein (DnaJ/Hsp40) molecular chaperone machinery, involved in cellular protein homeostasis, is being investigated as a novel drug target in various cellular systems including malaria. In Plasmodium the diverse chaperone complement is intimately involved in infected erythrocyte remodelling associated with the development and pathogenesis of malaria. In this review, we provide an overview of the Hsp70-J protein chaperone complement in Plasmodium falciparum and compare it with other Plasmodium species including the ones that serve as experimental study models for malaria. We propose that the unique traits possessed by this machinery not only provide avenues for drug targeting but also inform the evolutionary fitness of this parasite to its environment.

Keywords: Cell stress, drug targets, heat shock proteins, J proteins, Hsp70, malaria, molecular chaperones, Plasmodium, transmitting vectors, erythrocyte.

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Article Details

VOLUME: 19
ISSUE: 3
Year: 2013
Page: [387 - 403]
Pages: 17
DOI: 10.2174/1381612811306030387
Price: $65

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