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. 2020 Jan 18;9(1):245. doi: 10.3390/cells9010245

Figure 1.

Figure 1

Model for the role of the RhoA-ROCK pathway in the pathogenesis of TBI. The small GTPase RhoA is activated by RhoA-GEFs in response to various extracellular signals triggered by injury. Active GTP-bound RhoA binds to and stimulates the activity of the serine/threonine kinase ROCK1/2. Through phosphorylation of downstream effectors such as PTEN, LIMK, MLC, and CRMP-2, ROCK initiates signaling cascades that induce cytoskeletal remodeling underlying dendrite/axon retraction and synapse/spine loss as well as cell death, which together contribute to functional deficits. Inhibition of ROCK (e.g., Fasudil, Y-27632) or RhoA rescues these TBI-induced deficits. ROCK: Rho Kinase, GEF: guanine nucleotide exchange factor, GAP: GTPase-activating protein, GDI: Guanine nucleotide dissociation inhibitor, PTEN: phosphatase and tensin homolog, LIMK: LIM kinase, MLC: myosin light chain, CRMP2: collapsin response mediator protein 2, MAG: myelin-associated glycoprotein, OMgp: oligodendrocyte-myelin glycoprotein, NgR: nogo receptor, PTPσ: protein tyrosine phosphate σ, NgR1/3: nogo receptor 1 and 3, LAR: leukocyte common antigen-related phosphatase, CSPG: chondroitin sulfate proteoglycans.