Stem Cell and Cancer Research Institute, Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
Mol Autism. 2020 Apr 21;11(1):27. doi: 10.1186/s13229-020-00334-5.
Proteomics is the large-scale study of the total protein content and their overall function within a cell through multiple facets of research. Advancements in proteomic methods have moved past the simple quantification of proteins to the identification of post-translational modifications (PTMs) and the ability to probe interactions between these proteins, spatially and temporally. Increased sensitivity and resolution of mass spectrometers and sample preparation protocols have drastically reduced the large amount of cells required and the experimental variability that had previously hindered its use in studying human neurological disorders. Proteomics offers a new perspective to study the altered molecular pathways and networks that are associated with autism spectrum disorders (ASD). The differences between the transcriptome and proteome, combined with the various types of post-translation modifications that regulate protein function and localization, highlight a novel level of research that has not been appropriately investigated. In this review, we will discuss strategies using proteomics to study ASD and other neurological disorders, with a focus on how these approaches can be combined with induced pluripotent stem cell (iPSC) studies. Proteomic analysis of iPSC-derived neurons have already been used to measure changes in the proteome caused by patient mutations, analyze changes in PTMs that resulted in altered biological pathways, and identify potential biomarkers. Further advancements in both proteomic techniques and human iPSC differentiation protocols will continue to push the field towards better understanding ASD disease pathophysiology. Proteomics using iPSC-derived neurons from individuals with ASD offers a window for observing the altered proteome, which is necessary in the future development of therapeutics against specific targets.
蛋白质组学是通过多个研究方面来大规模研究细胞内总蛋白质含量及其整体功能。蛋白质组学方法的进步已经超越了蛋白质的简单定量，发展到了鉴定翻译后修饰（PTMs）以及探测这些蛋白质之间相互作用的能力，包括空间和时间上的相互作用。质谱仪和样品制备方案的灵敏度和分辨率的提高大大减少了所需细胞的大量数量和以前阻碍其在研究人类神经紊乱中的应用的实验可变性。蛋白质组学为研究与自闭症谱系障碍（ASD）相关的改变分子途径和网络提供了新视角。转录组和蛋白质组之间的差异，加上调节蛋白质功能和定位的各种类型的翻译后修饰，突出了一个尚未得到适当研究的新研究水平。在这篇综述中，我们将讨论使用蛋白质组学研究 ASD 和其他神经紊乱的策略，重点讨论这些方法如何与诱导多能干细胞（iPSC）研究相结合。已经使用 iPSC 衍生神经元的蛋白质组分析来测量由患者突变引起的蛋白质组变化，分析导致改变生物途径的 PTM 变化，并鉴定潜在的生物标志物。蛋白质组学技术和人类 iPSC 分化方案的进一步发展将继续推动该领域更好地了解 ASD 疾病病理生理学。使用来自 ASD 个体的 iPSC 衍生神经元进行蛋白质组学研究为观察改变的蛋白质组提供了一个窗口，这是针对特定靶标开发治疗方法的未来发展所必需的。
