Bromodomain protein 4 (BRD4) as a central epigenetic regulator in neuropsychiatric and neurodegenerative disorders

Bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal (BET) family, is a central epigenetic regulator that links histone acetylation-dependent chromatin remodelling to transcriptional control. Through recognition of acetylated lysine residues and recruitment of transcriptional machinery, it is increasingly recognised as a critical regulator of neuronal and glial functions, influencing synaptic plasticity, neuroinflammation, learning, memory, and behavioural adaptation. A wide range of neurological, neurodevelopmental, and neuropsychiatric diseases are linked to abnormal BRD4 signalling. BRD4 coordinates common pathogenic pathways, such as dysregulated transcriptional networks, by binding to acetylated histones and recruiting positive transcription elongation factor b to stimulate RNA polymerase II-dependent transcription of genes associated with central nervous system (CNS) diseases such as Alzheimer's and post-traumatic stress disorder. These convergent roles of BRD4 positioned it as a molecular hub that connects CNS dysfunction and epigenetic control. In this review, we focus on the involvement of BRD4 in various CNS disorders and provide a thorough overview of its structure, transcriptional mechanisms, and physiological and pathogenic functions in the CNS. Here, the emphasis is on common BRD4-dependent mechanisms that span multiple neurological conditions and the therapeutic opportunities and challenges associated with targeting BRD4. Collectively, current evidence supports BRD4 as a promising target for precision epigenetic therapies aimed at restoring neuronal homeostasis and modifying disease progression.