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蛋白质组学在精准医学中的新兴作用:在神经退行性疾病和神经创伤中的应用

The Emerging Role of Proteomics in Precision Medicine: Applications in Neurodegenerative Diseases and Neurotrauma.

作者信息

Alaaeddine Rana, Fayad Mira, Nehme Eliana, Bahmad Hisham F, Kobeissy Firas

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

Biomedical Engineering Program, Faculty of Engineering and Architecture and Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

出版信息

Adv Exp Med Biol. 2017;1007:59-70. doi: 10.1007/978-3-319-60733-7_4.

Abstract

Inter-individual variability in response to pharmacotherapy has provoked a higher demand to personalize medical decisions. As the field of pharmacogenomics has served to translate personalized medicine from concept to practice, the contribution of the "omics" disciplines to the era of precision medicine seems to be vital in improving therapeutic outcomes. Although we have observed significant advances in the field of genomics towards personalized medicine , the field of proteomics-with all its capabilities- is still in its infancy towards the area of personalized precision medicine. Neurodegenerative diseases and neurotrauma are among the areas where the implementation of neuroproteomics approaches has enabled neuroscientists to broaden their understanding of neural disease mechanisms and characteristics. It has been shown that the influence of epigenetics, genetics and environmental factors were among the recognized factors contributing to the diverse presentation of a single disease as well as its treatment establishing the factor-disease interaction. Thus, management of these variable single disease presentation/outcome necessitated the need for factoring the influence of epigenetics, genetics, epigenetics, and other factors on disease progression to create a custom treatment plan unique to each individual. In fact, neuroproteomics with its high ability to decipher protein alterations along with their post translational modifications (PTMs) can be an ideal tool for personalized medicine goals including: discovery of molecular mechanisms underlying disease pathobiology, development of novel diagnostics, enhancement of pharmacological neurotherapeutic approaches and finally, providing a "proteome identity" for patients with certain disorders and diseases. So far, neuroproteomics approaches have excelled in the areas of biomarker discovery arena where several diagnostic, prognostic and injury markers have been identified with a direct impact on the neurodegenerative diseases and neurotrauma. However, other applications in proteomics such as "individual" proteome sequencing with its signature PTMs, have not been fully investigated as compared to the achievements in the genomics discipline This infers that proteomics research work has promising potential, yet to be discovered, in the precision medicine and comprises a major component of the personalized medicine infrastructure as it allows individual characterization of disease at the protein level. To conclude, the field of proteomics-based personalized medicine is still in its infancy compared to genomics field due to several technical and instrumentation-based obstacles; however, we anticipate to have this initiative leading in the coming future. This chapter will discuss briefly how neuroproteomics can impact personalized medicine in the fields of neurodegenerative disorders particularly in Alzheimer's disease and brain injury .

摘要

药物治疗反应的个体间差异引发了对个性化医疗决策的更高需求。随着药物基因组学领域将个性化医疗从概念转化为实践,“组学”学科对精准医学时代的贡献在改善治疗效果方面似乎至关重要。尽管我们已经观察到基因组学领域在个性化医疗方面取得了重大进展,但蛋白质组学及其所有功能在个性化精准医学领域仍处于起步阶段。神经退行性疾病和神经创伤是神经蛋白质组学方法得以应用的领域,使神经科学家能够拓宽对神经疾病机制和特征的理解。研究表明,表观遗传学、遗传学和环境因素的影响是导致单一疾病多种表现及其治疗差异的公认因素,这些因素相互作用。因此,应对这些单一疾病的可变表现/结果需要考虑表观遗传学、遗传学、表观遗传学和其他因素对疾病进展的影响,以制定针对每个个体的定制治疗方案。事实上,神经蛋白质组学凭借其解读蛋白质改变及其翻译后修饰(PTM)的强大能力,可能成为实现个性化医疗目标的理想工具,这些目标包括:发现疾病病理生物学的分子机制、开发新型诊断方法、增强药理学神经治疗方法,最终为患有某些疾病的患者提供“蛋白质组特征”。到目前为止,神经蛋白质组学方法在生物标志物发现领域表现出色,已经鉴定出多种对神经退行性疾病和神经创伤有直接影响的诊断、预后和损伤标志物。然而,与基因组学领域的成就相比,蛋白质组学的其他应用,如具有特征性PTM的“个体”蛋白质组测序,尚未得到充分研究。这表明蛋白质组学研究工作在精准医学中具有尚未被发掘的潜力,并且由于它能够在蛋白质水平上对疾病进行个体特征描述,因此是个性化医疗基础设施的重要组成部分。总之,由于一些基于技术和仪器的障碍,基于蛋白质组学的个性化医疗领域与基因组学领域相比仍处于起步阶段;然而,我们预计这一领域在未来将引领潮流。本章将简要讨论神经蛋白质组学如何在神经退行性疾病领域,特别是在阿尔茨海默病和脑损伤方面影响个性化医疗。

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