This suggests a strong translation of effect across species and increases our confidence that these notable miRNAs may be predictive biomarkers of chemical-induced neurodegeneration in nonclinical safety studies and in humans.Įlucidation of predictive fluidic biochemical markers to detect and monitor chemical-induced neurodegeneration has been a major challenge due to a lack of understanding of molecular mechanisms driving altered neuronal morphology and function, as well as poor sensitivity in methods to quantify low-level biomarkers in bodily fluids. Additionally, these miRNAs were previously shown to be altered in a variety of nonclinical systems, such as human neuroblastoma and neural progenitor cells, and nonclinical species including mice and rats under neurotoxic conditions (Aranha et al., 2010 Beveridge et al., 2009 Feng et al., 2020 Jeyaseelan et al., 2008 Jian et al., 2019 Jin et al., 2021 Liu et al., 2015 Shen et al., 2020 Song et al., 2019 Wang and Jia, 2021 Wang et al., 2016 Wang et al.,, 2020Wei et al., 2015 Yang et al., 2021 Zhang et al., 2014 Zhao et al., 2017Zhao et al.,, 2021Zhong et al., 2020). We specifically focused on secreted biomarkers in vitro, since secreted factors would be most likely to translate to detection of miRNAs in fluids (serum, CSF, and urine) of animals or humans. 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. Inhibiting the Rho/ROCK pathway with miRNAs alleviates apoptosis, neuroinflammation, oxidative stress, and axon growth inhibition in IS and SCI. Recently, it has been reported that miRNAs are decreased in IS and SCI, while lncRNAs are increased. 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. However, they have attracted much attention because they play an essential role in regulating gene expression in physiological and pathological conditions. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), were previously considered to be non-functional. 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. RhoA is a small GTPase protein that activates a downstream effector, ROCK. Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. In conclusion, miR-30b could be a novel target for sensation recovery after SCI. The agomir could also regulate Sema3A/NRP-1/PlexinA1/RhoA/ROCK axis in vivo and restore spinal cord sensory conductive function. Agomir promoted neurite growth in NogoA inhibitory conditions, which indicated miR-30b could both enhance neuronal intrinsic regenerative ability and promote neurite growth against inhibitory microenvironment via Sema3A/NRP-1/PlexinA1/RhoA/ROCK axis.
Neurite outgrowth that inhibited by sema3A and the miR-30b antagomir was increased by Y-27632. GTP-RhoA and ROCK expression were down-regulated by miR-30b. The neurite length was induced by the miR-30b agomir, and the application of sema3A protein could reverse the effect of agomir. MiR-30b regulated the formation of sema3A-NRP-1-PlexinA1 complex via targeting sema3A. MiR-30b targeted and degraded sema3A mRNA. The neurite growth was promoted by miR-30b agomir and inhibited by antagomir. We wondered whether miR-30b could promote primary sensory neuron (PSN) axon growth in inhibitory microenvironment. Spinal cord injury (SCI) induces both motor and sensory dysfunctions.
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