Presynaptic dysfunction in neurodevelopmental disorders: Insights from the synaptic vesicle life cycle

The activity-dependent fusion, retrieval and recycling of synaptic vesicles is essential for the maintenance of neurotransmission. Until relatively recently it was believed that most mutations in genes that were essential for this process would be incompatible with life, because of this fundamental role. However, an ever-expanding number of mutations in this very cohort of genes are being identified in individuals with neurodevelopmental disorders, including autism, intellectual disability and epilepsy. This article will summarize the current state of knowledge linking mutations in presynaptic genes to neurodevelopmental disorders by sequentially covering the various stages of the synaptic vesicle life cycle. It will also discuss how perturbations of specific stages within this recycling process could translate into human disease. Finally, it will also provide perspectives on the potential for future therapy that are targeted to presynaptic function.

Automated summary

The fusion, retrieval, and recycling of synaptic vesicles is crucial for neurotransmission maintenance. Mutations in presynaptic genes are increasingly linked to neurodevelopmental disorders such as autism, intellectual disability, and epilepsy. Understanding how mutations in different stages of the synaptic vesicle life cycle can lead to disease may guide future therapies targeting presynaptic function.