Title:Aim for the Readers! Bromodomains As New Targets Against Chagas’ Disease
Volume: 26
Issue: 36
Author(s): Victoria Lucia Alonso, Luis Emilio Tavernelli, Alejandro Pezza, Pamela Cribb, Carla Ritagliati and Esteban Serra*
Affiliation:
- Instituto de Biologia Molecular y Celular de Rosario (IBR-CONICET), Rosario,Argentina
Keywords:
Bromodomains, trypanosoma cruzi, acetylation, bromodomain inhibitors, chagas diseases, drug
discovery.
Abstract: Bromodomains recognize and bind acetyl-lysine residues present in histone and non-histone
proteins in a specific manner. In the last decade they have raised as attractive targets for drug discovery
because the miss-regulation of human bromodomains was discovered to be involved in the development
of a large spectrum of diseases. However, targeting eukaryotic pathogens bromodomains
continues to be almost unexplored. We and others have reported the essentiality of diverse bromodomain-
containing proteins in protozoa, offering a new opportunity for the development of antiparasitic
drugs, especially for Trypansoma cruzi, the causative agent of Chagas’ disease. Mammalian bromodomains
were classified in eight groups based on sequence similarity but parasitic bromodomains are very
divergent proteins and are hard to assign them to any of these groups, suggesting that selective inhibitors
can be obtained. In this review, we describe the importance of lysine acetylation and bromodomains
in T. cruzi as well as the current knowledge on mammalian bromodomains. Also, we summarize
the myriad of small-molecules under study to treat different pathologies and which of them have been
tested in trypanosomatids and other protozoa. All the information available led us to propose that
T. cruzi bromodomains should be considered as important potential targets and the search for smallmolecules
to inhibit them should be empowered.
