一种药物重定向方法揭示了可向的表观遗传通路在Plasmodium vivax的催眠菌中
Steven P Maher1, Malina A Bakowski2, Amélie Vantaux3
1Center for Tropical and Emerging Global Disease, University of Georgia, Athens, United States.
eLife
|September 30, 2025
概括
确定了针对肝脏阶段的新型抗疟疾药物,这些药物是Plasmodium vivax hypnozoites. 表观遗传抑制剂,包括DNA甲基转移酶和基因组修饰抑制剂,对催眠菌具有选择性活性,为彻底治愈疟疾提供了新的希望.
科学领域:
- 疟疾学 疟疾学
- 寄生虫学的寄生虫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 治疗Plasmodium vivax疟疾的根本方法需要消除肝脏阶段的hypnozoites.
- 目前的治疗方法对脆弱人群有禁忌.
- 迫切需要针对催眠症患者的新型治疗点.
研究的目的:
- 为了识别新的药物和药物标的Plasmodium vivax hypnozoites.
- 选表观遗传抑制剂对抗肝阶段寄生虫的活性.
- 调查表观遗传机制在催眠细胞持续性中的作用.
主要方法:
- 对ReFRAME库和表观遗传抑制剂对P. vivax肝脏阶段的查.
- 针对表观遗传途径的选择性抑制剂的鉴定.
- 通过免疫光和双硫酸盐测序,分析P. vivax肝体和脊髓体的DNA甲基化和基因组修饰.
主要成果:
- 表观遗传抑制剂,包括DNA甲基转移酶和基因素修饰抑制剂,对P. vivax和P. cynomolgi hypnozoites具有选择性的活性.
- 发现Plasmodium肝阶段寄生虫DNA是甲基化的,在大多数杂虫的编码基因中都有甲基化信号.
- 促进体区域和第一个外因子中的甲基化水平可能会影响P. vivax基因表达.
结论:
- 表观遗传机制可能调节催眠细胞的形成和持久性.
- 针对表观遗传特征的抑制剂是开发新抗疟疾药物的有希望的策略.
- 这项研究为发现改善P. vivax疟疾的激进治疗方法提供了基础.
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