Evaluation of curcumin and MG-132 effect on the parasite Schistosoma mansoni: a genomic approach

• Grant number: 09/11437-5
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2009
• End date: September 30, 2011
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Vanderlei Rodrigues
• Grantee: Vanderlei Rodrigues
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Schistosomiasis remains a severe health public problem in several developing countries. Uncountable reports show an increasing emergence of Schistosoma mansoni strains resistant to Praziquantel, the current drug of choice to the Schistosomiasis treatment. In this way, the development of new and efficient drugs against this parasitosis is indispensable. The effect of proteasome inhibitors, such as MG-132, has been reported in some protozoan parasites, not only on the proliferation inhibition but also on the cell cycle progression and replication blockage. In our studies, MG-132 has decreased the number of pulmonary stage schistosomula, the parasite burden, and consequently the oviposition in infected mice. Curcumin, phenolic compost deriving from Curcuma longa, has shown antitumor, anti-inflammatory, antiparasitic effect and inhibitory action on the proteasome activity. Recently, our group has demonstrated that curcumin causes the separation of adult worm couples of S. mansoni, eggs infertility, oviposition and parasite viability decreasing, leading to death. Like these composts are known to reduce direct (MG-132) and indirectly (curcumin) the proteasome activity and are able to modulate gene expression, we propose to investigate their effects on S. mansoni adult worm through microarray analyses, in order to understand better the signaling via of ubiquitin-proteasome complex in this parasite biology, as well as the possibility of analyzing new molecular alternative targets in therapeutics against Schistosomiasis. (AU)