Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Neurosurgery, Department of Surgery, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Mol Neurobiol. 2020 Jun;57(6):2702-2726. doi: 10.1007/s12035-020-01916-3. Epub 2020 Apr 23.
Degradomics is a proteomics sub-discipline whose goal is to identify and characterize protease-substrate repertoires. With the aim of deciphering and characterizing key signature breakdown products, degradomics emerged to define encryptic biomarker neoproteins specific to certain disease processes. Remarkable improvements in structural and analytical experimental methodologies as evident in research investigating cellular behavior in neuroscience and cancer have allowed the identification of specific degradomes, increasing our knowledge about proteases and their regulators and substrates along with their implications in health and disease. A physiologic balance between protein synthesis and degradation is sought with the activation of proteolytic enzymes such as calpains, caspases, cathepsins, and matrix metalloproteinases. Proteolysis is essential for development, growth, and regeneration; however, inappropriate and uncontrolled activation of the proteolytic system renders the diseased tissue susceptible to further neurotoxic processes. In this article, we aim to review the protease-substrate repertoires as well as emerging therapeutic interventions in spinal cord injury at the degradomic level. Several protease substrates and their breakdown products, essential for the neuronal structural integrity and functional capacity, have been characterized in neurotrauma including cytoskeletal proteins, neuronal extracellular matrix glycoproteins, cell junction proteins, and ion channels. Therefore, targeting exaggerated protease activity provides a potentially effective therapeutic approach in the management of protease-mediated neurotoxicity in reducing the extent of damage secondary to spinal cord injury.
降解组学是蛋白质组学的一个分支，其目的是鉴定和描述蛋白酶-底物库。为了解码和描述关键特征性降解产物，降解组学的出现定义了特定疾病过程特有的加密生物标志物新蛋白。神经科学和癌症领域细胞行为研究中结构和分析实验方法的显著改进，允许鉴定特定的降解组，增加了我们对蛋白酶及其调节剂和底物的了解，以及它们在健康和疾病中的意义。通过激活钙蛋白酶、半胱天冬酶、组织蛋白酶和基质金属蛋白酶等蛋白水解酶，寻求蛋白质合成和降解之间的生理平衡。蛋白水解对于发育、生长和再生至关重要；然而，蛋白水解系统的不适当和失控激活使患病组织易受进一步的神经毒性过程影响。本文旨在综述降解组学水平下脊髓损伤的蛋白酶-底物库以及新出现的治疗干预措施。已经在神经创伤中对几种蛋白酶底物及其降解产物进行了描述，这些产物对神经元结构完整性和功能能力至关重要，包括细胞骨架蛋白、神经元细胞外基质糖蛋白、细胞连接蛋白和离子通道。因此，靶向过度表达的蛋白酶活性为管理蛋白酶介导的神经毒性提供了一种潜在有效的治疗方法，可减少脊髓损伤后继发性损伤的程度。
