Abstract
A rational approach for developing effective filaricides awaits greater knowledge on the biochemical pathways operating in filarial parasites. For example, metabolic pathways or key enzymes that are so pivotal to the parasite that their interruption or inhibition causes spontaneous death, could be exploited to develop effective chemotherapeutic agents. Similarly, developing a safe and nontoxic filaricidal will require precise understanding of whether or not the potential molecular target in the parasite is unique or at least different enough from the host system. Recently, we identified a novel transglutaminase enzyme (EC2.3.2.13; TGase) in filarial parasites that plays an important role during their normal growth and development. Based on these principles, TGase may serve as a new target for the development of effective chemotherapeutic agent and vaccine for controlling and preventing the infections caused by these parasites.
Key Words: Filariasis, transglutaminase, chemotherapy, cuticle, sheath
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References
- 1.Mehta K., Rao U.R., Vickery A.C., Birckbichler P.J. Significance of transglutaminase-catalyzed reactions in growth and development of filarial parasite,B. malayi. Bicochem. Biophys. Res. Commun. 1990;225:625–634. doi: 10.1016/s0006-291x(05)80892-7. [DOI] [PubMed] [Google Scholar]
- 2.Mehta K., Rao U.R., Vickery A.C., Fesus L. Identification of a novel transglutaminase from the filarial parasiteB. malayi and its role in growth and development. Mol. Biochem. Parasitol. 1992;74:105–114. doi: 10.1016/0166-6851(92)90002-2. [DOI] [PubMed] [Google Scholar]
- 3.Singh R.N., Mehta K. Purification and characterization of a novel transglutaminase from filarial nematodeB. malayi. Eur. J. Biochem. 1994;225:625–634. doi: 10.1111/j.1432-1033.1994.00625.x. [DOI] [PubMed] [Google Scholar]
- 4.Sing R.N., Chandrashekar R., Mehta K. Purification and partial characterization of transglutaminase from dog filarial parasite,Dirofilaria immitis. Int. J. Bicochem. Cell Biol. 1995;27:1285–1291. doi: 10.1016/1357-2725(95)00102-U. [DOI] [PubMed] [Google Scholar]
- 5.Mehta K., Chandrashekar R., Rao U.R. Transglutaminase-catalyzed incorporation of host proteins inBrugia malayi microfilariae. Mol. Biochem. Parasitol. 1996;76:105–114. doi: 10.1016/0166-6851(95)02549-9. [DOI] [PubMed] [Google Scholar]
- 6.Lustigman S., Brotman B., Huima T., Castelhano A.L., Singh R.N., Mehta K., Prince A.M. Transglutaminase-catalyzed reaction is important for molting ofOnchocerca volvulus third-stage larvae. Antimicrob. Agents Chemother. 1995;39:1913–1919. doi: 10.1128/aac.39.9.1913. [DOI] [PMC free article] [PubMed] [Google Scholar]