Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
Int J Mol Sci. 2021 Oct 26;22(21):11573. doi: 10.3390/ijms222111573.
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.
缺血性中风 (IS) 和脊髓损伤 (SCI) 是导致残疾的主要原因。RhoA 是一种小 GTP 酶蛋白，可激活下游效应物 ROCK。RhoA/ROCK 通路的上调导致 IS 和 SCI 中的神经元凋亡、神经炎症、血脑屏障功能障碍、星形胶质细胞增生和轴突生长抑制。非编码 RNA（ncRNA），如 microRNAs（miRNAs）和长非编码 RNA（lncRNAs），以前被认为是无功能的。然而，它们在调节生理和病理条件下的基因表达方面发挥着重要作用，因此引起了广泛关注。越来越多的证据表明，ROCK 抑制剂，如 fasudil 和 VX-210，可减少动物模型和临床试验中的 IS 和 SCI 损伤。最近有报道称，miRNAs 在 IS 和 SCI 中减少，而 lncRNAs 增加。用 miRNAs 抑制 Rho/ROCK 通路可减轻 IS 和 SCI 中的细胞凋亡、神经炎症、氧化应激和轴突生长抑制。需要进一步研究以探讨 ncRNA 在 IS 和 SCI 中的意义，并为预防和治疗这些毁灭性疾病建立新的策略。
