Anne Lespine, Clara Blancfuney, Roger Prichard, Mélanie Alberich
{"title":"P-glycoproteins in anthelmintic safety, efficacy, and resistance.","authors":"Anne Lespine, Clara Blancfuney, Roger Prichard, Mélanie Alberich","doi":"10.1016/j.pt.2024.07.008","DOIUrl":null,"url":null,"abstract":"<p><p>P-glycoprotein (PGP) is a pivotal transmembrane transporter governing the cellular flux of diverse substances shielding mammals from toxics. It can thwart the effectiveness of medicines such as ivermectin (IVM) and other macrocyclic lactone (ML) anthelmintics, undermining therapeutic efforts. We analyze the role of PGPs in limiting the toxicity of these drugs in hosts, and their potential contribution to anthelmintic resistance in nematodes. Targeting nematode PGPs to increase drug sensitivity to MLs seems interesting, but is hampered by the lack of selective inhibitors. The nuclear hormone receptor (NHR)-8 should be seriously considered as a target because it upregulates multiple PGPs involved in anthelmintic resistance and it is specific to nematodes. This would advance our understanding of host-pathogen dynamics and foster innovative therapeutic strategies.</p>","PeriodicalId":23327,"journal":{"name":"Trends in parasitology","volume":null,"pages":null},"PeriodicalIF":7.0000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in parasitology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.pt.2024.07.008","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PARASITOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
P-glycoprotein (PGP) is a pivotal transmembrane transporter governing the cellular flux of diverse substances shielding mammals from toxics. It can thwart the effectiveness of medicines such as ivermectin (IVM) and other macrocyclic lactone (ML) anthelmintics, undermining therapeutic efforts. We analyze the role of PGPs in limiting the toxicity of these drugs in hosts, and their potential contribution to anthelmintic resistance in nematodes. Targeting nematode PGPs to increase drug sensitivity to MLs seems interesting, but is hampered by the lack of selective inhibitors. The nuclear hormone receptor (NHR)-8 should be seriously considered as a target because it upregulates multiple PGPs involved in anthelmintic resistance and it is specific to nematodes. This would advance our understanding of host-pathogen dynamics and foster innovative therapeutic strategies.
期刊介绍：
Since its inception as Parasitology Today in 1985, Trends in Parasitology has evolved into a highly esteemed review journal of global significance, reflecting the importance of medical and veterinary parasites worldwide. The journal serves as a hub for communication among researchers across all disciplines of parasitology, encompassing endoparasites, ectoparasites, transmission vectors, and susceptible hosts.
Each monthly issue of Trends in Parasitology offers authoritative, cutting-edge, and yet accessible review articles, providing a balanced and comprehensive overview, along with opinion pieces offering personal and novel perspectives. Additionally, the journal publishes a variety of short articles designed to inform and stimulate thoughts in a lively and widely-accessible manner. These include Science & Society (discussing the interface between parasitology and the general public), Spotlight (highlighting recently published research articles), Forum (presenting single-point hypotheses), Parasite/Vector of the Month (featuring a modular display of the selected species), Letter (providing responses to recent articles in Trends in Parasitology), and Trendstalk (conducting interviews). Please note that the journal exclusively publishes literature reviews based on published data, with systematic reviews, meta-analysis, and unpublished primary research falling outside our scope.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
