Protein Degradome of Spinal Cord Injury: Biomarkers and Potential Therapeutic Targets
| Autor: | Shadi Bsat, Edwyn Jeremy Assaf, Howard L. Weiner, Stefania Mondello, Hadi Abou-El-Hassan, Kevin K.W. Wang, Firas Kobeissy, Ibrahim Omeis, Fares Sukhon |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteomics Proteases Proteome medicine.medical_treatment Proteolysis Neuroscience (miscellaneous) Spinal cord injury Mass Spectrometry 03 medical and health sciences Cellular and Molecular Neuroscience Biomarkers Breakdown Degradomics Protease 0302 clinical medicine medicine Animals Humans Caspase Spinal Cord Injuries Neurons biology medicine.diagnostic_test Regeneration (biology) Proteolytic enzymes Calpain Cell biology 030104 developmental biology Neurology biology.protein Protein Processing Post-Translational 030217 neurology & neurosurgery |
| Zdroj: | Molecular neurobiology. 57(6) |
| ISSN: | 1559-1182 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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