Jane J Pappas, Rita Khoueiry, Lode Godderis, Zdenko Herceg
{"title":"The epigenetic mechanisms mediating the long-term impacts of toxicants on brain functions and health.","authors":"Jane J Pappas, Rita Khoueiry, Lode Godderis, Zdenko Herceg","doi":"10.1016/B978-0-443-19043-8.00021-9","DOIUrl":null,"url":null,"abstract":"<p><p>Recent advances in toxicoepigenetics have significantly enhanced our understanding of epigenetic modifications induced by toxicant exposures. This review synthesizes current knowledge regarding epigenetic alterations - primarily DNA methylation, histone acetylation, and miRNA perturbations - associated with common toxicants, including arsenic, lead, methylmercury, formaldehyde, α-hexabromocyclododecane, bisphenol A, and fluoxetine. While substantial evidence derives from rodent models, human studies have made crucial contributions by characterizing toxicant-specific epigenetic signatures, identifying affected genes and pathways, and establishing epigenetic regulation as a critical mediator of biologic responses. This review highlights parallels between toxicant-induced epigenetic changes and those observed in neurologic disorders, particularly focusing on the potential of epigenetic marks as early diagnostic tools for synaptic dysfunction in Alzheimer disease, but also focusing on Huntington disease and Parkinson disease. It relies on evidence ranging from exposures in vitro and in vivo (mainly in rodents) to human exposures. It also highlights parallels between toxicant-induced epigenetic changes and those observed in brain cancers. The findings underscore the therapeutic potential of targeting epigenetic mechanisms to mitigate toxicant-induced neurologic effects. We conclude by proposing a strategic framework for further advancing toxicoepigenetic research, emphasizing the creation of a centralized databank for toxicant-induced brain epigenetic alterations, the development of validated epigenetic bioassays, and the integration of functional neuroimaging. Our proposed comprehensive approach, combining genetics, toxicology, epidemiology, and environmental science, aims to inform and enhance risk assessment protocols and therapeutic interventions.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"449-481"},"PeriodicalIF":0.0000,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Handbook of clinical neurology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/B978-0-443-19043-8.00021-9","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Recent advances in toxicoepigenetics have significantly enhanced our understanding of epigenetic modifications induced by toxicant exposures. This review synthesizes current knowledge regarding epigenetic alterations - primarily DNA methylation, histone acetylation, and miRNA perturbations - associated with common toxicants, including arsenic, lead, methylmercury, formaldehyde, α-hexabromocyclododecane, bisphenol A, and fluoxetine. While substantial evidence derives from rodent models, human studies have made crucial contributions by characterizing toxicant-specific epigenetic signatures, identifying affected genes and pathways, and establishing epigenetic regulation as a critical mediator of biologic responses. This review highlights parallels between toxicant-induced epigenetic changes and those observed in neurologic disorders, particularly focusing on the potential of epigenetic marks as early diagnostic tools for synaptic dysfunction in Alzheimer disease, but also focusing on Huntington disease and Parkinson disease. It relies on evidence ranging from exposures in vitro and in vivo (mainly in rodents) to human exposures. It also highlights parallels between toxicant-induced epigenetic changes and those observed in brain cancers. The findings underscore the therapeutic potential of targeting epigenetic mechanisms to mitigate toxicant-induced neurologic effects. We conclude by proposing a strategic framework for further advancing toxicoepigenetic research, emphasizing the creation of a centralized databank for toxicant-induced brain epigenetic alterations, the development of validated epigenetic bioassays, and the integration of functional neuroimaging. Our proposed comprehensive approach, combining genetics, toxicology, epidemiology, and environmental science, aims to inform and enhance risk assessment protocols and therapeutic interventions.
期刊介绍：
The Handbook of Clinical Neurology (HCN) was originally conceived and edited by Pierre Vinken and George Bruyn as a prestigious, multivolume reference work that would cover all the disorders encountered by clinicians and researchers engaged in neurology and allied fields. The first series of the Handbook (Volumes 1-44) was published between 1968 and 1982 and was followed by a second series (Volumes 45-78), guided by the same editors, which concluded in 2002. By that time, the Handbook had come to represent one of the largest scientific works ever published. In 2002, Professors Michael J. Aminoff, François Boller, and Dick F. Swaab took on the responsibility of supervising the third (current) series, the first volumes of which published in 2003. They have designed this series to encompass both clinical neurology and also the basic and clinical neurosciences that are its underpinning. Given the enormity and complexity of the accumulating literature, it is almost impossible to keep abreast of developments in the field, thus providing the raison d''être for the series. The series will thus appeal to clinicians and investigators alike, providing to each an added dimension. Now, more than 140 volumes after it began, the Handbook of Clinical Neurology series has an unparalleled reputation for providing the latest information on fundamental research on the operation of the nervous system in health and disease, comprehensive clinical information on neurological and related disorders, and up-to-date treatment protocols.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
