Hindley Nicole, Sanchez Avila Anna, Henstridge Christopher
Division of Cellular and Systems Medicine, University of Dundee, Dundee, United Kingdom.
Euan Macdonald Centre for Motor Neuron Disease, University of Edinburgh, Edinburgh, United Kingdom.
Front Synaptic Neurosci. 2023 Mar 15;15:1130198. doi: 10.3389/fnsyn.2023.1130198. eCollection 2023.
Synapses are integral for healthy brain function and are becoming increasingly recognized as key structures in the early stages of brain disease. Understanding the pathological processes driving synaptic dysfunction will unlock new therapeutic opportunities for some of the most devastating diseases of our time. To achieve this we need a solid repertoire of imaging and molecular tools to interrogate synaptic biology at greater resolution. Synapses have historically been examined in small numbers, using highly technical imaging modalities, or in bulk, using crude molecular approaches. However, recent advances in imaging techniques are allowing us to analyze large numbers of synapses, at single-synapse resolution. Furthermore, multiplexing is now achievable with some of these approaches, meaning we can examine multiple proteins at individual synapses in intact tissue. New molecular techniques now allow accurate quantification of proteins from isolated synapses. The development of increasingly sensitive mass-spectrometry equipment means we can now scan the synaptic molecular landscape almost in totality and see how this changes in disease. As we embrace these new technical developments, synapses will be viewed with clearer focus, and the field of synaptopathy will become richer with insightful and high-quality data. Here, we will discuss some of the ways in which synaptic interrogation is being facilitated by methodological advances, focusing on imaging, and mass spectrometry.
突触对于健康的大脑功能至关重要，并且越来越被视为脑部疾病早期阶段的关键结构。了解导致突触功能障碍的病理过程将为我们这个时代一些最具毁灭性的疾病带来新的治疗机会。为了实现这一目标，我们需要一系列可靠的成像和分子工具，以便以更高的分辨率研究突触生物学。从历史上看，对突触的研究要么是使用高技术含量的成像方式少量进行，要么是使用粗略的分子方法大量进行。然而，成像技术的最新进展使我们能够以单突触分辨率分析大量突触。此外，现在其中一些方法可以实现多重分析，这意味着我们可以在完整组织中的单个突触处检测多种蛋白质。新的分子技术现在能够对分离出的突触中的蛋白质进行精确量化。日益灵敏的质谱设备的发展意味着我们现在几乎可以全面扫描突触分子图谱，并了解其在疾病中的变化情况。随着我们采用这些新的技术发展，突触将得到更清晰的关注，并且突触病领域将因富有洞察力的高质量数据而更加丰富。在此，我们将讨论方法学进展促进突触研究的一些方式，重点是成像和质谱。
