Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, SI-1000, Ljubljana, Slovenia.
International Postgraduate School Jožef Stefan, SI-1000, Ljubljana, Slovenia.
Proteomics Clin Appl. 2019 Nov;13(6):e1800138. doi: 10.1002/prca.201800138. Epub 2019 Jul 22.
The upregulation of protease expression and proteolytic activity is implicated in numerous pathological conditions such as neurodegeneration, cancer, cardiovascular and autoimmune diseases, and bone degeneration. During disease progression, various proteases form characteristic patterns of cleaved proteins and peptides, which can affect disease severity and course of progression. It has been shown that qualitative and quantitative monitoring of cleaved protease substrates can provide relevant prognostic, diagnostic, and therapeutic information. As proteolytic fragments and peptides generated in the affected tissue are commonly translocated to blood, urine, and other proximal fluids, their possible application as biomarkers is the subject of ongoing research. The field of degradomics has been established to enable the global identification of proteolytic events on the organism level, utilizing proteomic approaches and sample preparation techniques that facilitate the detection of proteolytic processing of protease substrates in complex biological samples. In this review, some of the latest developments in degradomic methodologies used for the identification and validation of biologically relevant proteolytic events and their application in the search for clinically relevant biomarker candidates are presented. The current state of degradomics in clinics is discussed and the future perspectives of the field are outlined.
蛋白酶表达和活性的上调与许多病理状况有关，如神经退行性疾病、癌症、心血管和自身免疫性疾病以及骨退化。在疾病进展过程中，各种蛋白酶形成特征性的切割蛋白和肽模式，这可能会影响疾病的严重程度和进展过程。已经表明，定性和定量监测切割蛋白酶底物可以提供相关的预后、诊断和治疗信息。由于在受影响的组织中产生的蛋白水解片段和肽通常转移到血液、尿液和其他近端液体中，因此它们作为生物标志物的可能应用是正在进行的研究的主题。降解组学领域的建立是为了能够在生物体水平上对蛋白水解事件进行全面鉴定，利用蛋白质组学方法和样品制备技术来促进对复杂生物样品中蛋白酶底物蛋白水解加工的检测。本文介绍了一些最新的降解组学方法学进展，用于鉴定和验证具有生物学意义的蛋白水解事件，并将其应用于寻找具有临床意义的生物标志物候选物的研究中。本文还讨论了降解组学在临床中的现状，并概述了该领域的未来展望。
