title: Neuroproteomics approach and neurosystems biology analysis: ROCK inhibitors as promising therapeutic targets in neurodegeneration and neurotrauma.
abstract: Several common degenerative mechanisms and mediators underlying the neuronal injury pathways characterize several neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's disease, as well as brain neurotrauma. Such common ground invites the emergence of new approaches and tools to study the altered pathways involved in neural injury alongside with neuritogenesis, an intricate process that commences with neuronal differentiation. Achieving a greater understanding of the impaired pathways of neuritogenesis would significantly help in uncovering detailed mechanisms of axonal regeneration. Among the several agents involved in neuritogenesis are the Rho and Rho kinases (ROCKs), which constitute key integral points in the Rho/ROCK pathway that is known to be disrupted in multiple neuropathologies such as spinal cord injury, traumatic brain injury, and Alzheimer's disease. This in turn renders ROCK inhibition as a promising candidate for therapeutic targets for treatment of neurodegenerative diseases. Among the novel tools to investigate the mechanisms involved in a specific disorder is the use of neuroproteomics/systems biology approach, a growing subfield of bioinformatics aiming to study and establishing a global assessment of the entire neuronal proteome, addressing the dynamic protein changes and interactions. This review aims to examine recent updates regarding how neuroproteomics aids in the understanding of molecular mechanisms of activation and inhibition in the area of neurogenesis and how Rho/ROCK pathway/ROCK inhibitors, primarily Y-27632 and Fasudil compounds, are applied in biological settings, promoting neuronal survival and neuroprotection that has direct future implications in neurotrauma.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Raad
authors.forename: Tala
authors.initials: T
authors.lastname: El Tal
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Gul
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Rose-Mary
authors.initials: RM
authors.lastname: Boustany
authors.forename: Joy
authors.initials: J
authors.lastname: Guingab
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Wang
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D040901:Proteomics / Q000379:methods*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases