Publication: Las enzimas desubiquitinadoras como dianas de moléculas pequeñas en kinetoplástidos
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2018-09-21
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Universidad Complutense de Madrid
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Abstract
Millones de personas sufren y más de 1000 millones están en riesgo de contraer la tripanosomiasis Africana, el mal de Chagas o la leishmaniasis. Estas enfermedades son causadas por los kinetoplástidos Trypanosoma brucei, T. cruzi y Leishmania spp., respectivamente. Los tratamientos actualmente disponibles para estas enfermedades son viejos y poseen perfiles complejos de administración, baja eficacia y/o serios efectos adversos. Además, los parásitos causantes están desarrollando resistencias a los tratamientos existentes. Por estas razones hay una necesidad urgente de descubrir nuevos tratamientos para estas dolencias. Es por tanto importante enfocarse en nuevas dianas que demuestren ser tratables. La maquinaria de ubiquitina ofrece una oportunidad excitante como diana para el desarrollo de nuevas terapias. Las desubiquitinasas son enzimas responsables de retirar moléculas de ubiquitina de proteínas diana y regulan numerosos procesos celulares. Estas enzimas ya están siendo exploradas como dianas en otras áreas terapéuticas. Recientemente se ha demostrado que algunas desubiquitinasas son esenciales en T. brucei. Los 3 parásitos tienen genomas y biologías similares (El-Sayed et al., 2005). Así, cabe esperar que las moléculas que modulen una diana conservada sean activas frente a los 3 patógenos (Khare et al., 2016)...
Millions of people suffer from and more than 1 billion people live at the risk of contracting human African trypanosomiasis (HAT), Chagas disease and leishmaniasis. These diseases are caused by Trypanosoma brucei, T. cruzi and Leishmania spp. respectively - members of the class Kinetoplastida. The current treatments against these diseases are old and have complex administration profiles, low efficacy and/or serious side effects. The causative parasites are also developing resistance against the available treatments. Therefore, there is an urgent need to discover new treatments for these diseases. For this it is important to focus on new targets that have proven to be tractable. The ubiquitin machinery provides an exciting opportunity as the target for development of new therapies. Deubiquitinases are the enzymes responsible for removing ubiquitin from target proteins and regulate a whole lot of cellular processes. They are being pursued as targets in several therapeutic areas. It was shown that some deubiquitinases are essential in T. brucei. The three parasites have similar genomic sequence and biology (El-Sayed et al., 2005). Thus compounds targeting a conserved target could be active against all three parasites (Khare et al., 2016)...
Millions of people suffer from and more than 1 billion people live at the risk of contracting human African trypanosomiasis (HAT), Chagas disease and leishmaniasis. These diseases are caused by Trypanosoma brucei, T. cruzi and Leishmania spp. respectively - members of the class Kinetoplastida. The current treatments against these diseases are old and have complex administration profiles, low efficacy and/or serious side effects. The causative parasites are also developing resistance against the available treatments. Therefore, there is an urgent need to discover new treatments for these diseases. For this it is important to focus on new targets that have proven to be tractable. The ubiquitin machinery provides an exciting opportunity as the target for development of new therapies. Deubiquitinases are the enzymes responsible for removing ubiquitin from target proteins and regulate a whole lot of cellular processes. They are being pursued as targets in several therapeutic areas. It was shown that some deubiquitinases are essential in T. brucei. The three parasites have similar genomic sequence and biology (El-Sayed et al., 2005). Thus compounds targeting a conserved target could be active against all three parasites (Khare et al., 2016)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 9-05-2017