作为药物靶点的转录因子和染色质修饰剂

Luisa Fernanda Ortega Sepulveda, Gabriela Mendes de Oliveira, Elaine Hellen Nunes Chagas, Nele Wild, Franciarli Silva da Paz, Carsten Wrenger, Gerhard Wunderlich
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引用次数: 0

摘要

疟原虫复杂的生命周期要求疟原虫充分适应不同的条件。因此,疟原虫严格控制其基因表达,考虑到其与人类宿主的进化距离,相关因素可能成为有吸引力的潜在药物靶点。近年来,一些独特的转录因子和染色质修饰因子已经在恶性疟原虫和鼠种P. yoelii和P. berghei中被鉴定和部分表征。本文综述了针对神秘的植物样ap2转录因子和染色质修饰剂(如组蛋白乙酰转移酶和去乙酰化酶、组蛋白甲基转移酶和去甲基化酶)的药物开发的研究数据。考虑到已报道的抑制这两个因素的成功,这些因素可以作为通过干扰其对基因表达的控制来有效对抗寄生虫的靶标。
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Plasmodial Transcription Factors and Chromatin Modifiers as Drug Targets
The complex life cycle of the malaria parasite Plasmodium requires the parasite to adequately adapt to different conditions. For this reason, Plasmodium strictly controls its gene expression, and given its evolutionary distance from the human host, the involved factors may figure as attractive potential drug targets. In recent years, several unique transcription factors and chromatin modifiers have been identified and partially characterized in Plasmodium falciparum and in the murine species P. yoelii and P. berghei. This review unites data from studies focusing on drug development against enigmatic plant-like AP2-transcription factors and chromatin modifiers, such as histone acetyl transferases and deacetylases and histone methyltransferases and demethylases. Considering the reported success of inhibition of both factors, these may be included as targets to effectively combat the parasite by perturbing its control of gene expression.
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