Centre for Discovery Brain Sciences, University of Edinburgh, Scotland, UK.
J Neurochem. 2021 Apr;157(2):107-129. doi: 10.1111/jnc.15316. Epub 2021 Mar 16.
Over the course of the last few decades it has become clear that many neurodevelopmental and neurodegenerative disorders have a synaptic defect, which contributes to pathogenicity. A rise in new techniques, and in particular '-omics'-based methods providing large datasets, has led to an increase in potential proteins and pathways implicated in synaptic function and related disorders. Additionally, advancements in imaging techniques have led to the recent discovery of alternative modes of synaptic vesicle recycling. This has resulted in a lack of clarity over the precise role of different pathways in maintaining synaptic function and whether these new pathways are dysfunctional in neurodevelopmental and neurodegenerative disorders. A greater understanding of the molecular detail of pre-synaptic function in health and disease is key to targeting new proteins and pathways for novel treatments and the variety of new techniques currently available provides an ideal opportunity to investigate these functions. This review focuses on techniques to interrogate pre-synaptic function, concentrating mainly on synaptic vesicle recycling. It further examines techniques to determine the underlying molecular mechanism of pre-synaptic dysfunction and discusses methods to identify molecular targets, along with protein-protein interactions and cellular localization. In combination, these techniques will provide an expanding and more complete picture of pre-synaptic function. With the application of recent technological advances, we are able to resolve events with higher spatial and temporal resolution, leading research towards a greater understanding of dysfunction at the presynapse and the role it plays in pathogenicity.
在过去的几十年中，人们已经清楚地认识到许多神经发育和神经退行性疾病都存在突触缺陷，这导致了疾病的发生。新技术的兴起，特别是基于“组学”的方法提供了大量数据集，导致了与突触功能和相关疾病相关的潜在蛋白质和途径的增加。此外，成像技术的进步导致了最近发现了突触囊泡再循环的替代模式。这导致了人们对于不同途径在维持突触功能中的精确作用以及这些新途径在神经发育和神经退行性疾病中是否失调缺乏清晰的认识。深入了解健康和疾病中突触前功能的分子细节是靶向新蛋白质和途径以进行新治疗的关键，目前各种新技术提供了一个理想的机会来研究这些功能。本综述重点介绍了研究突触前功能的技术，主要集中在突触囊泡再循环上。它进一步探讨了确定突触前功能障碍的潜在分子机制的技术，并讨论了识别分子靶标以及蛋白质-蛋白质相互作用和细胞定位的方法。这些技术的结合将提供一个不断扩展和更完整的突触前功能图。随着最近技术进步的应用，我们能够以更高的时空分辨率解决事件，使研究能够更好地理解突触前的功能障碍及其在发病机制中的作用。
