Targeting heat shock protein 90 for malaria.
Heat shock protein 90 (Hsp90), an ATP-dependent molecular chaperone, is a highly conserved and ubiquitously expressed stress protein in eukaryotes. It is responsible for activation of various proteins involved in signal transduction, cell cycle control, hormone signaling, and transcription. Anomalous expression of this family can be associated with several disease states. Current article focuses on the novel use of Hsp90 inhibitors as antimalarial agents. The present armamentarium of antimalarial therapy is not proving itself as an adequate treatment to eradicate malaria completely. This inadequacy is mainly due to the increasing drug resistance rate in Plasmodium species. The parasite Plasmodium falciparum requires Hsp90 (Pfhsp90) for regulating its development. Analysis of PfHsp90 function suggests that it regulates parasite development during the frequent febrile episodes that are characteristic of malaria. This crucial role of Hsp90 in the growth and development of the parasite has attracted many researchers as a potential target for malaria and other infectious diseases. Currently there are about seven antimalarial and more than thirty anticancer Hsp90 inhibitors in various phases of drug development. Addition of alternatives with novel mechanism to the current treatment armoury may eventually help improve the outcomes of malaria. It is prudent to remain optimistic as the research in this field continues to evolve.
Departments of Pharmaceutical Chemistry and Pharmaceutical Biotechnology, SPP School of Pharmacy and Technology Management, SVKM's NMIMS, V. L. Mehta Road, Vile Parle (West), Mumbai-400056, India. prashant.kharkar@nmims.edu.
Anup S
AS
Ramdhave
Dhaval
D
Patel
I
I
Ramya
Mukesh
M
Nandave
Prashant S
PS
Kharkar
D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000378:metabolism; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods*
D000962:Antimalarials; D018841:HSP90 Heat-Shock Proteins