{"title":"Mechanisms of organophosphate neurotoxicity","authors":"Yi-Hua Tsai, Pamela J. Lein","doi":"10.1016/j.cotox.2021.04.002","DOIUrl":null,"url":null,"abstract":"<div><p><span>The canonical mechanism of organophosphate<span> (OP) neurotoxicity is the inhibition of </span></span>acetylcholinesterase<span> (AChE). However, multiple lines of evidence suggest that mechanisms in addition to or other than AChE inhibition contribute to the neurotoxic effects associated with acute and chronic OP exposures. Characterizing the role(s) of AChE inhibition versus noncholinergic mechanisms in OP neurotoxicity remains an active area of research with significant diagnostic and therapeutic implications. Here, we review recently published studies that provide mechanistic insights regarding (1) OP-induced status epilepticus, (2) long-term neurologic consequences of acute OP exposures, and (3) neurotoxic effects associated with repeated low-level OP exposures. Key data gaps and challenges are also discussed.</span></p></div>","PeriodicalId":37736,"journal":{"name":"Current Opinion in Toxicology","volume":"26 ","pages":"Pages 49-60"},"PeriodicalIF":2.4000,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cotox.2021.04.002","citationCount":"27","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Toxicology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468202021000152","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/4/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 27
Abstract
The canonical mechanism of organophosphate (OP) neurotoxicity is the inhibition of acetylcholinesterase (AChE). However, multiple lines of evidence suggest that mechanisms in addition to or other than AChE inhibition contribute to the neurotoxic effects associated with acute and chronic OP exposures. Characterizing the role(s) of AChE inhibition versus noncholinergic mechanisms in OP neurotoxicity remains an active area of research with significant diagnostic and therapeutic implications. Here, we review recently published studies that provide mechanistic insights regarding (1) OP-induced status epilepticus, (2) long-term neurologic consequences of acute OP exposures, and (3) neurotoxic effects associated with repeated low-level OP exposures. Key data gaps and challenges are also discussed.
期刊介绍:
The aims and scope of Current Opinion in Toxicology is to systematically provide the reader with timely and provocative views and opinions of the highest qualified and recognized experts on current advances in selected topics within the field of toxicology. The goal is that Current Opinion in Toxicology will be an invaluable source of information and perspective for researchers, teachers, managers and administrators, policy makers and students. Division of the subject into sections: For this purpose, the scope of Toxicology is divided into six selected high impact themed sections, each of which is reviewed once a year: Mechanistic Toxicology, Metabolic Toxicology, Risk assessment in Toxicology, Genomic Toxicology, Systems Toxicology, Translational Toxicology.