Synaptic Vesicle Cycle: From Mechanistic Insights to Epigenetic Perspectives

The synaptic vesicle cycle is a critical process that ensures efficient neurotransmission across synaptic junctions, facilitating proper communication within the neuronal circuits. This cycle comprises several tightly regulated steps, including vesicle biogenesis, fusion with the presynaptic membrane, recycling, and degradation, all of which are essential for maintaining synaptic function. Specialized proteins orchestrate the molecular machinery responsible for coordinating vesicle trafficking throughout each stage of the cycle. In recent years, research has highlighted the emerging role of epigenetic regulation in modulating the synaptic vesicle cycle. Epigenetic modifications, such as DNA methylation, histone acetylation, and microRNA expression, regulate vesicle dynamics by modulating key stages of the vesicle trafficking cycle, that in turn affects neurotransmitter release and synaptic plasticity. These regulatory mechanisms ensure synaptic health and proper neuronal communication, while their disruption has been linked to synaptopathies, including autism, schizophrenia, Parkinson's, and Alzheimer's diseases. By examining both molecular and epigenetic factors, this review provides valuable insights into how gene expression and protein function are intricately involved in the regulation of the synaptic vesicle cycle. It highlights the importance of key events in regulating the synaptic vesicle cycle, their potential epigenetic drivers, and their relevance to addressing synaptic dysfunctions in various neurological disorders.