MicroRNA-128–3p as a promising target in neuropsychiatric disorders: From epigenetics to pharmacological intervention

Major depressive disorder (MDD) is a leading neuropsychiatric condition associated with significant morbidity and mortality worldwide. Epigenetic mechanisms are key factors involved in the development of MDD, with microRNAs (miRNAs) serving as important epigenetic regulators in this process. Increasing evidence suggests that approximately 70 % of miRNA is expressed in the brain, playing a crucial role in various brain functions. Aberrant changes in miRNA expression are frequently associated with the pathophysiology of stress-related neuropsychiatric disorders, including MDD. One notable stress-responsive miRNA is miR-128, which is highly expressed in the brain and involved in numerous functions, such as neural development, signaling pathways, neuronal migration, neural plasticity, and neurogenesis. The significant role of this miRNA positions it as a critical candidate for increased susceptibility to stress. So far, the role of miR-128 has been reported in various neurodegenerative disorders; however, studies examining its involvement in neuropsychiatric disorders are gaining traction. More specifically, miR-128 has been shown to influence the Wnt signaling pathway, potentially leading to depression-like behavior. In this review, we critically evaluate the functions of miR-128, with a particular focus on its regulatory mechanisms, target gene expression, and downstream signaling pathways. Additionally, we provide a comprehensive assessment of miR-128–3p regarding its potential involvement in the pathogenesis of MDD and its possible role as a disease and treatment biomarker. This exploration may unveil new avenues for innovative diagnostic approaches and treatment strategies in MDD. • Stress contributes to the development of MDD with epigenetic changes at the level of miRNAs. • miR-128, a brain-enriched miRNA, is strongly associated with stress responses and MDD. • Aberrant miR-128 expression disrupts neural plasticity, signaling networks, and neurogenesis. • By influencing Wnt signaling, miR-128 has been linked to depression-related behaviors. • miR-128–3p is now recognized as a promising biomarker and potential therapeutic target for MDD.