Alternative splicing in serotonergic system: Implications in neuropsychiatric disorders

Background: The serotonergic system is a key component of physiological brain function and is essential for proper neurological activity. Numerous neuropsychiatric disorders are associated with deregulation of the serotonergic system. Accordingly, many pharmacological treatments are focused on modulation of this system. While providing a promising line of therapeutic moderation, these approaches may be complicated due to the presence of alternative splicing events for key genes in this pathway. Alternative splicing is a co-transcriptional process by which different mRNA transcripts can be produced from the same gene. These different isoforms may have diverse activities and functions, and their relative balance is often critical for the maintenance of homeostasis. Alternative splicing greatly increases the production of proteins, augmenting cell plasticity, and provides an important control point for regulation of gene expression. Aim: The objective of this narrative review is to discuss the potential impact of alternative splicing of different components of the serotonergic system and speculate on their involvement in several neuropsychiatric disorders. Conclusions: The specific role of each isoform in disease and their relative activities in the signalling pathways involved are yet to be determined. We need to gain a better understanding of the basis of alternative isoforms of the serotonergic system in order to fully understand their impact and be able to develop new effective pharmacological isoform-specific targets.