吡喹酮:其抗血吸虫病作用机制的最新进展及新的治疗前景

IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular and biochemical parasitology Pub Date : 2022-11-01 DOI:10.1016/j.molbiopara.2022.111531
Ranielly Araujo Nogueira , Maria Gabriela Sampaio Lira , Irlla Correia Lima Licá , Gleycka Cristine Carvalho Gomes Frazão , Vitor Augusto Ferreira dos Santos , Antonio Camilo Correia Mendes Filho , João Gustavo Mendes Rodrigues , Guilherme Silva Miranda , Rafael Cardoso Carvalho , Flávia Raquel Fernandes Nascimento
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引用次数: 7

摘要

吡喹酮(PZQ)是治疗所有形式血吸虫病的首选药物,尽管其作用机制尚不完全清楚。PZQ主要作用于成虫。本文叙述了PZQ在体外和体内对血吸虫的作用机制,并强调了该药物在寄生虫中的分子靶点和在最终宿主中诱导的免疫反应。此外,还讨论了PZQ的新的治疗用途。研究表明,除了影响电压操作的Ca2 +通道外,PZQ还可能与其他血吸虫分子相互作用,如肌球蛋白调节轻链、谷胱甘肽s -转移酶和瞬时受体电位通道。PZQ给药后,观察到T调节性1型(Tr1)细胞分化增加,炎症减少,表明PZQ促进了免疫调节途径。尽管PZQ广泛用于大规模给药计划,但尚未证实存在耐药寄生虫;然而,这是一个值得关注的问题,应该在人群中不断进行调查。此外,我们还讨论了评估PZQ(除蠕虫感染外)的健康应用的研究,例如它在癌症治疗中的作用和它在病毒疫苗中的辅助作用。
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Praziquantel: An update on the mechanism of its action against schistosomiasis and new therapeutic perspectives

Praziquantel (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis, although its mechanisms of action are not completely understood. PZQ acts largely on adult worms. This narrative literature review describes what is known about the mechanisms of action of PZQ against schistosomes from in vitro and in vivo studies and highlights the molecular targets in parasites and immune responses induced in definitive hosts by this drug. Moreover, new therapeutic uses of PZQ are discussed. Studies have demonstrated that in addition to impacting voltage-operated Ca2 + channels, PZQ may interact with other schistosome molecules, such as myosin regulatory light chain, glutathione S-transferase, and transient receptor potential channels. Following PZQ administration, increased T regulatory type 1 (Tr1) cell differentiation and decreased inflammation were observed, indicating that PZQ promotes immunoregulatory pathways. Although PZQ is widely used in mass drug administration schemes, the existence of resistant parasites has not been proven; however, it is a concern that should be constantly investigated in human populations. In addition, we discuss studies that evaluate health applications of PZQ (other than helminth infection), such as its effect in cancer therapy and its adjuvant action in vaccines against viruses.

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来源期刊
CiteScore
2.90
自引率
0.00%
发文量
51
审稿时长
63 days
期刊介绍: The journal provides a medium for rapid publication of investigations of the molecular biology and biochemistry of parasitic protozoa and helminths and their interactions with both the definitive and intermediate host. The main subject areas covered are: • the structure, biosynthesis, degradation, properties and function of DNA, RNA, proteins, lipids, carbohydrates and small molecular-weight substances • intermediary metabolism and bioenergetics • drug target characterization and the mode of action of antiparasitic drugs • molecular and biochemical aspects of membrane structure and function • host-parasite relationships that focus on the parasite, particularly as related to specific parasite molecules. • analysis of genes and genome structure, function and expression • analysis of variation in parasite populations relevant to genetic exchange, pathogenesis, drug and vaccine target characterization, and drug resistance. • parasite protein trafficking, organelle biogenesis, and cellular structure especially with reference to the roles of specific molecules • parasite programmed cell death, development, and cell division at the molecular level.
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