Abou-El-Hassan Hadi, Sukhon Fares, Assaf Edwyn Jeremy, Bahmad Hisham, Abou-Abbass Hussein, Jourdi Hussam, Kobeissy Firas H
Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Faculty of Medicine, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Methods Mol Biol. 2017;1598:65-99. doi: 10.1007/978-1-4939-6952-4_4.
Degradomics has recently emerged as a subdiscipline in the omics era with a focus on characterizing signature breakdown products implicated in various disease processes. Driven by promising experimental findings in cancer, neuroscience, and metabolomic disorders, degradomics has significantly promoted the notion of disease-specific "degradome." A degradome arises from the activation of several proteases that target specific substrates and generate signature protein fragments. Several proteases such as calpains, caspases, cathepsins, and matrix metalloproteinases (MMPs) are involved in the pathogenesis of numerous diseases that disturb the physiologic balance between protein synthesis and protein degradation. While regulated proteolytic activities are needed for development, growth, and regeneration, uncontrolled proteolysis initiated under pathological conditions ultimately culminates into apoptotic and necrotic processes. In this chapter, we aim to review the protease-substrate repertoires in neural injury concentrating on traumatic brain injury. A striking diversity of protease substrates, essential for neuronal and brain structural and functional integrity, namely, encryptic biomarker neoproteins, have been characterized in brain injury. These include cytoskeletal proteins, transcription factors, cell cycle regulatory proteins, synaptic proteins, and cell junction proteins. As these substrates are subject to proteolytic fragmentation, they are ceaselessly exposed to activated proteases. Characterization of these molecules allows for a surge of "possible" therapeutic approaches of intervention at various levels of the proteolytic cascade.
降解组学最近在组学时代作为一个子学科出现，专注于表征与各种疾病过程相关的标志性降解产物。在癌症、神经科学和代谢紊乱方面有前景的实验结果的推动下，降解组学显著促进了疾病特异性“降解组”的概念。降解组源于几种蛋白酶的激活，这些蛋白酶靶向特定底物并产生标志性蛋白质片段。几种蛋白酶，如钙蛋白酶、半胱天冬酶、组织蛋白酶和基质金属蛋白酶（MMPs），参与了许多疾病的发病机制，这些疾病扰乱了蛋白质合成与蛋白质降解之间的生理平衡。虽然发育、生长和再生需要受调控的蛋白水解活性，但在病理条件下引发的不受控制的蛋白水解最终会导致凋亡和坏死过程。在本章中，我们旨在综述神经损伤，尤其是创伤性脑损伤中的蛋白酶-底物库。在脑损伤中已经鉴定出了对神经元和脑结构及功能完整性至关重要的蛋白酶底物的惊人多样性，即加密生物标志物新蛋白。这些包括细胞骨架蛋白、转录因子、细胞周期调节蛋白、突触蛋白和细胞连接蛋白。由于这些底物会发生蛋白水解片段化，它们不断暴露于活化的蛋白酶中。对这些分子的表征使得在蛋白水解级联反应的各个水平上有大量“可能”的治疗干预方法。
