Department of Biotechnology, Vellore Institute of Technology, Vellore, Tamil Nadu, India, 632014.
University of Sharjah, College of Health Sciences, and Research Institute for Medical and Health Sciences, Department of Medical Laboratory Sciences, University City, 27272, Sharjah, United Arab Emirates.
Mol Neurobiol. 2024 Jan;61(1):91-103. doi: 10.1007/s12035-023-03562-x. Epub 2023 Aug 16.
Synapses are the cellular substrates of higher-order brain functions, and their dysfunction is an early and primary pathogenic mechanism across several neurological disorders. In particular, Alzheimer's disease (AD) is categorized by prodromal structural and functional synaptic deficits, prior to the advent of classical behavioral and pathological features. Recent research has shown that the development, maintenance, and plasticity of synapses depend on localized protein translation. Synaptosomes and synaptoneurosomes are biochemically isolated synaptic terminal preparations which have long been used to examine a variety of synaptic processes ex vivo in both healthy and pathological conditions. These ex vivo preparations preserve the mRNA species and the protein translational machinery. Hence, they are excellent in organello tools for the study of alterations in mRNA levels and protein translation in neuropathologies. Evaluation of synapse-specific basal and activity-driven de novo protein translation activity can be conveniently performed in synaptosomal/synaptoneurosomal preparations from both rodent and human brain tissue samples. This review gives a quick overview of the methods for isolating synaptosomes and synaptoneurosomes before discussing the studies that have utilized these preparations to study localized synapse-specific protein translation in (patho)physiological situations, with an emphasis on AD. While the review is not an exhaustive accumulation of all the studies evaluating synaptic protein translation using the synaptosomal model, the aim is to assemble the most relevant studies that have done so. The hope is to provide a suitable research platform to aid neuroscientists to utilize the synaptosomal/synaptoneurosomal models to evaluate the molecular mechanisms of synaptic dysfunction within the specific confines of mRNA localization and protein translation research.
突触是大脑高级功能的细胞基础，其功能障碍是几种神经退行性疾病的早期和主要致病机制。特别是阿尔茨海默病（AD），其在出现典型的行为和病理特征之前，就表现出了早期的结构和功能突触缺陷。最近的研究表明，突触的发育、维持和可塑性依赖于局部蛋白质翻译。突触体和突触神经小体是从生物化学上分离出来的突触末端制剂，长期以来一直被用于在健康和病理条件下研究各种突触过程的体外实验。这些体外制剂保留了 mRNA 种类和蛋白质翻译机制。因此，它们是研究神经病理学中 mRNA 水平和蛋白质翻译变化的极好的细胞器工具。在来自啮齿动物和人类脑组织样本的突触体/突触神经小体制剂中，可以方便地评估突触特异性基础和活性驱动的从头蛋白质翻译活性。本文首先简要概述了分离突触体和突触神经小体的方法，然后讨论了利用这些制剂在（病理）生理条件下研究局部突触特异性蛋白质翻译的研究，重点是 AD。虽然这篇综述并不是评估使用突触体模型进行突触蛋白翻译的所有研究的详尽积累，但目的是汇集最相关的研究。希望提供一个合适的研究平台，帮助神经科学家利用突触体/突触神经小体模型，在 mRNA 定位和蛋白质翻译研究的特定范围内，评估突触功能障碍的分子机制。
