Abstract
Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. RhoA is a small GTPase protein that activates a downstream effector, ROCK. The up-regulation of the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, and axon growth inhibition in IS and SCI. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), were previously considered to be non-functional. However, they have attracted much attention because they play an essential role in regulating gene expression in physiological and pathological conditions. There is growing evidence that ROCK inhibitors, such as fasudil and VX-210, can reduce injury in IS and SCI in animal models and clinical trials. Recently, it has been reported that miRNAs are decreased in IS and SCI, while lncRNAs are increased. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Further studies are required to explore the significance of ncRNAs in IS and SCI and to establish new strategies for preventing and treating these devastating diseases.
Highlights
Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability worldwide
The clinical utility of Micro RNAs (miRNAs) will be very high if they can be delivered in the form of extracellular vesicles, as shown by Jia et al [123]
The Rho/Rho-associated coiled-coil protein kinase (ROCK) pathway is deeply involved in IS and SCI in various ways, including apoptosis, neuroinflammation, BBB integrity, astrogliosis, axonal regeneration, neurogenesis, and angiogenesis
Summary
Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability worldwide. MiRNAs and lncRNAs have gained much attention in recent years because they play essential roles in many biological functions and are deeply involved in various pathological conditions, including ischemia-reperfusion injuries [8]. ROCK transcript is prominently expressed in non-neuronal tissues, light chain (MLC), myosin light chain phosphatase (MLCP), LIM kinase, ezrin/rawhile is present more abundantly in the brain and skeletal muscle. ROCK regulates smooth muscle contraction, cytoskeletal rearrangement via (MLC), myosin light chain phosphatase (MLCP), LIM kinase, ezrin/radixin/moesin (ERM), stress fiber formation, focalresponse adhesion, actin protein filament stabilization, growth cone collapsin mediator. The inhibition of ROCK significantly reduced focal adhesion trocytes, suggestingand thestress importance of theinduced pathway the processes involved fiber formation by Thy-1. RhoGEF: Rho guanine nucleotide factor; light chain; ERM: ezrin/radixin/moesin; LIMK: LIM kinase; CRMP2: collapsin responseexchange mediator protein
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