Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (Fiocruz), Manguinhos, Rio de Janeiro, Brazil.
Laboratory of Gene Expression Regulation, Carlos Chagas Institute, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil.
J Mol Neurosci. 2019 Jan;67(1):150-164. doi: 10.1007/s12031-018-1220-1. Epub 2018 Dec 15.
Alzheimer's disease, Parkinson's disease, prion diseases, schizophrenia, and multiple sclerosis are the most common nervous system diseases, affecting millions of people worldwide. The current scientific literature associates these pathological conditions to abnormal expression levels of certain proteins, which in turn improved the knowledge concerning normal and affected brains. However, there is no available cure or preventive therapy for any of these disorders. Proteogenomics is a recent approach defined as the data integration of both nucleotide high-throughput sequencing and protein mass spectrometry technologies. In the last years, proteogenomics studies in distinct diseases have emerged as a strategy for the identification of uncharacterized proteoforms, which are all the different protein forms derived from a single gene. For many of these diseases, at least one protein used as biomarker presents more than one proteoform, which fosters the analysis of publicly available data focusing proteoforms. Given this context, we describe the most important biomarkers for each neurodegenerative disease and how genomics, transcriptomics, and proteomics separately contributed to unveil them. Finally, we present a selection of proteogenomics studies in which the combination of nucleotide and proteome high-throughput data, from cell lines or brain tissue samples, is used to uncover proteoforms not previously described. We believe that this new approach may improve our knowledge about nervous system diseases and brain function and an opportunity to identify new biomarker candidates.
阿尔茨海默病、帕金森病、朊病毒病、精神分裂症和多发性硬化症是最常见的神经系统疾病，影响着全球数百万人。目前的科学文献将这些病理状况与某些蛋白质的异常表达水平联系起来，这反过来又提高了对正常和受影响大脑的认识。然而，这些疾病目前还没有有效的治疗方法或预防疗法。蛋白质基因组学是一种新的方法，定义为核苷酸高通量测序和蛋白质质谱技术数据的整合。在过去几年中，不同疾病的蛋白质基因组学研究已成为鉴定未表征的蛋白质形式的一种策略，这些蛋白质形式均来自单个基因。对于许多这些疾病，至少有一种用作生物标志物的蛋白质具有一种以上的蛋白质形式，这促进了针对蛋白质形式的公共可用数据的分析。鉴于这种情况，我们描述了每种神经退行性疾病的最重要的生物标志物，以及基因组学、转录组学和蛋白质组学如何分别有助于揭示它们。最后，我们介绍了一些蛋白质基因组学研究，其中组合使用核苷酸和蛋白质组高通量数据（来自细胞系或脑组织样本）来揭示以前未描述的蛋白质形式。我们相信，这种新方法可以提高我们对神经系统疾病和大脑功能的认识，并为发现新的生物标志物候选物提供机会。
