动体寄生虫的表观遗传景观：从组蛋白翻译后修饰到新兴的治疗策略。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-09-27 DOI:10.1016/j.bmc.2025.118377

Inès Jacquet , Romain Paoli-Lombardo , Patrice Vanelle , Nicolas Primas

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引用次数: 0

摘要

着丝质体是引起各种被忽视的热带病的寄生虫。它们基因组组成的一个标志性特征是存在多顺反子转录，这是一种涉及多个基因转录成单个mRNA分子的现象，伴随着非常规的基因调控模式。在这些生物体中，组蛋白变异和翻译后修饰在调节染色质结构和转录活性方面起着关键作用。本文综述了在利什曼原虫、克氏锥虫和布鲁氏锥虫中发现的组蛋白变异和翻译后修饰，详细介绍了修饰的多样性及其已知的功能作用。本综述还将重点关注书写蛋白、擦除蛋白和读取蛋白，包括现有的三维结构数据，以更好地了解它们对染色质调控、细胞周期进程和寄生虫适应的贡献。同时，这篇综述提供了针对这些途径的治疗努力的概要，强调了计算机、体外和体内研究的结果。这一全面的综述强调了解开着丝质体表观遗传机制的潜力，作为开发针对这些主要人类病原体的创新治疗方法的有希望的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The epigenetic landscape of kinetoplastid parasites: From histone post-translational modifications to emerging therapeutic strategies

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The epigenetic landscape of kinetoplastid parasites: From histone post-translational modifications to emerging therapeutic strategies

Kinetoplastids are parasites which cause various neglected tropical diseases. A hallmark feature of their genomic composition is the presence of polycistronic transcription, a phenomenon that involves the transcription of multiple genes into a single mRNA molecule, along with unconventional modes of gene regulation. In these organisms, histone variants and post-translational modifications play pivotal roles in modulating chromatin structure and transcriptional activity. This review provides a comprehensive overview of histone variants and post-translational modifications identified across Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei, detailing both the diversity of modifications and their known functional roles. This review also focuses on the writers, erasers, and readers proteins, including available three-dimensional structural data, to better understand their contribution to chromatin regulation, cell cycle progression, and parasite adaptation. Concurrently, this review offers a synopsis of therapeutic endeavors that have targeted these pathways, emphasizing the outcomes of in silico, in vitro and in vivo studies. This comprehensive review underscores the potential of unraveling kinetoplastid epigenetic mechanisms as a promising avenue for developing innovative treatments against these major human pathogens.

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.