Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, UK.
J Neurochem. 2021 Apr;157(2):179-207. doi: 10.1111/jnc.15035. Epub 2020 Jul 2.
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.
突触囊泡的活动依赖性融合、回收和再循环对于维持神经传递至关重要。直到最近，人们还认为，由于这个基本作用，对这个过程至关重要的基因突变大多数都是与生命不相容的。然而，在患有神经发育障碍的个体中，包括自闭症、智力残疾和癫痫，越来越多的此类基因中的突变正在被识别。本文将通过依次涵盖突触囊泡生命周期的各个阶段，总结将突触前基因中的突变与神经发育障碍联系起来的最新知识状态。它还将讨论在这个回收过程中的特定阶段的干扰如何转化为人类疾病。最后，它还将提供针对突触前功能的潜在未来治疗的视角。
