Soto Altea, Nieto-Díaz Manuel, Reigada David, Barreda-Manso María Asunción, Muñoz-Galdeano Teresa, Maza Rodrigo M
Molecular Neuroprotection Group, Research Unit, National Hospital for Paraplegics (SESCAM), 45071 Toledo, Spain.
Pharmaceuticals (Basel). 2022 Apr 25;15(5):529. doi: 10.3390/ph15050529.
Nogo-A protein is a key myelin-associated inhibitor of axonal growth, regeneration, and plasticity in the central nervous system (CNS). Regulation of the Nogo-A/NgR1 pathway facilitates functional recovery and neural repair after spinal cord trauma and ischemic stroke. MicroRNAs are described as effective tools for the regulation of important processes in the CNS, such as neuronal differentiation, neuritogenesis, and plasticity. Our results show that miR-182-5p mimic specifically downregulates the expression of the luciferase reporter gene fused to the mouse Nogo-A 3'UTR, and Nogo-A protein expression in Neuro-2a and C6 cells. Finally, we observed that when rat primary hippocampal neurons are co-cultured with C6 cells transfected with miR-182-5p mimic, there is a promotion of the outgrowth of neuronal neurites in length. From all these data, we suggest that miR-182-5p may be a potential therapeutic tool for the promotion of axonal regeneration in different diseases of the CNS.
Nogo-A蛋白是中枢神经系统(CNS)中轴突生长、再生和可塑性的关键髓磷脂相关抑制因子。Nogo-A/NgR1通路的调节有助于脊髓损伤和缺血性中风后的功能恢复和神经修复。微小RNA被认为是调节中枢神经系统重要过程(如神经元分化、神经突形成和可塑性)的有效工具。我们的结果表明,miR-182-5p模拟物特异性下调与小鼠Nogo-A 3'UTR融合的荧光素酶报告基因的表达,以及Neuro-2a和C6细胞中Nogo-A蛋白的表达。最后,我们观察到,当大鼠原代海马神经元与转染了miR-182-5p模拟物的C6细胞共培养时,神经元神经突的长度会增加。基于所有这些数据,我们认为miR-182-5p可能是促进中枢神经系统不同疾病中轴突再生的潜在治疗工具。