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新兴治疗靶点针对:DNA 修复反应抑制剂和遗传毒性药物的最新进展。

Emerging Therapeutic Targets Against : Update on DNA Repair Response Inhibitors and Genotoxic Drugs.

机构信息

Laboratorio de Parasitología Molecular, Instituto Tecnológico Chascomús (INTECH), Consejo Nacional de Investigaciones Científicas (CONICET)-Universidad Nacional General San Martin (UNSAM), Chascomús, Argentina.

Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States.

出版信息

Front Cell Infect Microbiol. 2020 Jun 12;10:289. doi: 10.3389/fcimb.2020.00289. eCollection 2020.

Abstract

is the causative agent of toxoplasmosis in animals and humans. This infection is transmitted to humans through oocysts released in the feces of the felines into the environment or by ingestion of undercooked meat. This implies that toxoplasmosis is a zoonotic disease and is a foodborne pathogen. In addition, chronic toxoplasmosis in goats and sheep is the cause of recurrent abortions with economic losses in the sector. It is also a health problem in pets such as cats and dogs. Although there are therapies against this infection in its acute stage, they are not able to permanently eliminate the parasite and sometimes they are not well tolerated. To develop better, safer drugs, we need to elucidate key aspects of the biology of . In this review, we will discuss the importance of the homologous recombination repair (HRR) pathway in the parasite's lytic cycle and how components of these processes can be potential molecular targets for new drug development programs. In that sense, the effect of different DNA damage agents or HHR inhibitors on the growth and replication of will be described. Multitarget drugs that were either associated with other targets or were part of general screenings are included in the list, providing a thorough revision of the drugs that can be tested in other scenarios.

摘要

弓形虫是动物和人类弓形虫病的病原体。这种感染通过猫科动物粪便中释放到环境中的卵囊或食用未煮熟的肉传播给人类。这意味着弓形虫病是一种人畜共患病,也是一种食源性病原体。此外,山羊和绵羊的慢性弓形虫病是导致该行业反复流产和经济损失的原因。它也是猫和狗等宠物的健康问题。虽然在急性阶段有针对这种感染的治疗方法,但它们不能永久消除寄生虫,有时也不能很好地耐受。为了开发更好、更安全的药物,我们需要阐明 的生物学的关键方面。在这篇综述中,我们将讨论同源重组修复(HRR)途径在寄生虫裂解周期中的重要性,以及这些过程的成分如何成为新药物开发计划的潜在分子靶点。在这种意义上,将描述不同的 DNA 损伤剂或 HHR 抑制剂对 的生长和复制的影响。列出了与其他靶点相关或作为一般筛选一部分的多靶点药物,对可在其他情况下进行测试的药物进行了全面审查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4b/7325978/cb5f3db98c8b/fcimb-10-00289-g0001.jpg

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