Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenida Brasil 4365, 21040-360 Manguinhos, RJ, Brazil.
Biomed Res Int. 2014;2014:614014. doi: 10.1155/2014/614014. Epub 2014 Mar 31.
The pathogenic trypanosomatids Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. are the causative agents of African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. These diseases are considered to be neglected tropical illnesses that persist under conditions of poverty and are concentrated in impoverished populations in the developing world. Novel efficient and nontoxic drugs are urgently needed as substitutes for the currently limited chemotherapy. Trypanosomatids display a single mitochondrion with several peculiar features, such as the presence of different energetic and antioxidant enzymes and a specific arrangement of mitochondrial DNA (kinetoplast DNA). Due to mitochondrial differences between mammals and trypanosomatids, this organelle is an excellent candidate for drug intervention. Additionally, during trypanosomatids' life cycle, the shape and functional plasticity of their single mitochondrion undergo profound alterations, reflecting adaptation to different environments. In an uncoupling situation, the organelle produces high amounts of reactive oxygen species. However, these species role in parasite biology is still controversial, involving parasite death, cell signalling, or even proliferation. Novel perspectives on trypanosomatid-targeting chemotherapy could be developed based on better comprehension of mitochondrial oxidative regulation processes.
致病性原生动物布氏锥虫、克氏锥虫和利什曼原虫分别是引起非洲锥虫病、恰加斯病和利什曼病的病原体。这些疾病被认为是被忽视的热带病，在贫困条件下持续存在，并集中在发展中国家的贫困人群中。由于目前的化疗药物有限，因此迫切需要新型高效、低毒的药物来替代。原生动物只含有一个线粒体，具有几个特殊的特征，例如存在不同的能量和抗氧化酶以及线粒体 DNA（动基体 DNA）的特定排列。由于哺乳动物和原生动物之间的线粒体差异，这个细胞器是药物干预的理想候选对象。此外，在原生动物的生命周期中，其单个线粒体的形状和功能可塑性会发生深刻的变化，以适应不同的环境。在解偶联的情况下，细胞器会产生大量的活性氧物质。然而，这些物质在寄生虫生物学中的作用仍然存在争议，涉及寄生虫的死亡、细胞信号转导，甚至增殖。基于对线粒体氧化调节过程的更好理解，可能会开发出针对原生动物的靶向化疗的新视角。
