Function of long-noncoding RNAs and microRNAs in the immune response and metabolism during Leishmania infection and the interference in the metabolism as new therapeutic strategy

Abstract

Understanding as parasite and host factors contribute to the pathogenesis of leishmaniasis is highly relevant to understanding the modulation of macrophage activation mediated by long noncoding RNA (lncRNA) and microRNAs (miRNAs). They can influence the transcriptional and post-transcriptional regulation of genes that can promote the survival or death of the parasite. The lncRNAs regulate the chromosomal structure, mRNA transcription, protein splicing, and translation. miRNAs regulate the translation and degradation of the target gene transcript by interacting with the 3'UTR region of the mRNA. The miRNAs and LncRNAs altered in Leishmania-infected macrophages can mediate the activation of the pro-inflammatory response or subversion of the host response to the parasite. The project's main objective is to evaluate the role of lncRNA, miRNAs in the regulation of the immune response and metabolism of macrophages infected with Leishmania and to use metabolic interference as a therapeutic strategy. Part 1 of the project will study the expression of lncRNAs, miRNAs, and correlated genes (host-genes) to elucidate the signals that regulate the activation of macrophages infected by L. amazonensis and L. infantum. In part 2 of the project, we will evaluate the leishmanicidal activity of new drugs developed to block the PEX5-14 interaction and localization of enzymes in the glycosome in promastigote forms and in vitro and in vivo models of infection with Leishmania. These drugs affect the transport of enzymes to the glycosome, impair the parasite's metabolism, leading to its death. By identifying possible prognostic markers and possible new treatments, we hope to better management of leishmaniasis. (AU)