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Apoptosis-like death in trypanosomatids: search for putative pathways and genes involved

机译:锥虫病中的细胞凋亡样死亡:寻找可能的通路和涉及的基因

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摘要

Members of the Trypanosomatidae family comprises species that are causative of important human diseases such as Chagas'disease, Leishmaniasis and sleeping sickness. A wealth of evidence has accumulated that illustrates the ability of these unicellular organisms to undergo, with or without induction (stress conditions), a cell death with some features resembling apoptosis-like phenomenon. However, despite the apparent phenotypic similarities between the apoptosis-like death of kinetoplastids and mammalian nucleated cell programmed cell death (PCD), the pathways seem to differ significantly. This review analyses some of the current data related to the cell death in trypanosomatids. Special attention is given to members of conserved protein families demonstrating remarkable diversity and plasticity of function [i.e. elongation factor-1 subunits α and γ ; and the Silent Information Regulator (SIR2)-related gene, showed to be associated with resistance to apoptosis-like death in Leishmania]. The elucidation of the molecular events which tightly regulated the processes of growth arrest, differentiation and death of Trypanosoma cruzi, Leishmania spp and African trypanosomes, might allow not only to define a more comprehensive view of the cell death machinery in term of evolutionary origin but may also be useful to identify new target molecules for chemotherapeutic drug development and therapeutic intervention.
机译:锥虫科的成员包括引起重要人类疾病的物种,如南美锥虫病,利什曼病和昏睡病。积累了大量的证据,说明了这些单细胞生物在有或没有诱导(应激条件)的情况下经历细胞死亡的能力,细胞死亡的某些特征类似于凋亡样现象。然而,尽管在运动质体的凋亡样死亡与哺乳动物有核细胞程序性细胞死亡(PCD)之间存在明显的表型相似性,但这些途径似乎存在显着差异。这篇评论分析了一些与锥虫的细胞死亡有关的当前数据。特别注意保守的蛋白质家族成员,这些成员表现出显着的功能多样性和可塑性[即延伸因子1亚基α和γ;和沉默信息调节因子(SIR2)相关基因,与利什曼原虫对凋亡样死亡的抗性有关。对分子事件的阐明可以严密调节克氏锥虫,利什曼原虫和非洲锥虫的生长停滞,分化和死亡的过程,这可能不仅可以从进化起源的角度更全面地了解细胞死亡机制,而且可以还可用于鉴定新的靶分子,用于化学治疗药物的开发和治疗干预。

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