{"title":"Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders.","authors":"Malak Hajar, Tobias Werner, Mihajlo Gajic, Holger Stark, Bassem Sadek","doi":"10.1002/med.22119","DOIUrl":null,"url":null,"abstract":"<p><p>Neuropsychiatric disorders present a multifaceted challenge, characterized by cognitive, social, and motor impairments with manifold underlying mechanisms. Recent attention has turned to epigenetic mechanisms, particularly histone lysine methyltransferases (HKMTs), such as G9a, in understanding fundamental pathogenesis. This review provides a concise overview of the structural and functional features of G9a and its involvement in neuropsychiatric disorders, including neurodevelopmental disorders (NDDs) like autism spectrum disorders (ASD) and Prader-Willi syndrome (PWS), schizophrenia (SZ), epilepsy, anxiety, depression, and Alzheimer's disease (AD). Furthermore, it highlights the biochemical mechanisms of G9a-mediated histone methylations and explores pharmacological interventions targeting G9a for potential therapeutic avenues. This current knowledge underlines G9a's significance as a therapeutic target and sets the stage for future investigations into its role in neuropsychiatric disorders.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":10.9000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medicinal Research Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/med.22119","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Neuropsychiatric disorders present a multifaceted challenge, characterized by cognitive, social, and motor impairments with manifold underlying mechanisms. Recent attention has turned to epigenetic mechanisms, particularly histone lysine methyltransferases (HKMTs), such as G9a, in understanding fundamental pathogenesis. This review provides a concise overview of the structural and functional features of G9a and its involvement in neuropsychiatric disorders, including neurodevelopmental disorders (NDDs) like autism spectrum disorders (ASD) and Prader-Willi syndrome (PWS), schizophrenia (SZ), epilepsy, anxiety, depression, and Alzheimer's disease (AD). Furthermore, it highlights the biochemical mechanisms of G9a-mediated histone methylations and explores pharmacological interventions targeting G9a for potential therapeutic avenues. This current knowledge underlines G9a's significance as a therapeutic target and sets the stage for future investigations into its role in neuropsychiatric disorders.
期刊介绍：
Medicinal Research Reviews is dedicated to publishing timely and critical reviews, as well as opinion-based articles, covering a broad spectrum of topics related to medicinal research. These contributions are authored by individuals who have made significant advancements in the field.
Encompassing a wide range of subjects, suitable topics include, but are not limited to, the underlying pathophysiology of crucial diseases and disease vectors, therapeutic approaches for diverse medical conditions, properties of molecular targets for therapeutic agents, innovative methodologies facilitating therapy discovery, genomics and proteomics, structure-activity correlations of drug series, development of new imaging and diagnostic tools, drug metabolism, drug delivery, and comprehensive examinations of the chemical, pharmacological, pharmacokinetic, pharmacodynamic, and clinical characteristics of significant drugs.
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