Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders

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.