Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Pres. Antônio Carlos, 6627, Belo Horizonte 31279-901, Brazil.
Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31279-901, Brazil.
Int J Mol Sci. 2024 Aug 21;25(16):9057. doi: 10.3390/ijms25169057.
Neurodegenerative disorders, including traumatic injuries to the central nervous system (CNS) and neurodegenerative diseases, are characterized by early axonal damage, which does not regenerate in the adult mammalian CNS, leading to permanent neurological deficits. One of the primary causes of the loss of regenerative ability is thought to be a developmental decline in neurons' intrinsic capability for axon growth. Different molecules are involved in the developmental loss of the ability for axon regeneration, including many transcription factors. However, the function of microRNAs (miRNAs), which are also modulators of gene expression, in axon re-growth is still unclear. Among the various miRNAs recently identified with roles in the CNS, miR-17, which is highly expressed during early development, emerges as a promising target to promote axon regeneration. Here, we used adeno-associated viral (AAV) vectors to overexpress miR-17 (AAV.miR-17) in primary cortical neurons and evaluate its effects on neurite and axon regeneration in vitro. Although AAV.miR-17 had no significant effect on neurite outgrowth and arborization, it significantly enhances neurite regeneration after scratch lesion and axon regeneration after axotomy of neurons cultured in microfluidic chambers. Target prediction and functional annotation analyses suggest that miR-17 regulates gene expression associated with autophagy and cell metabolism. Our findings suggest that miR-17 promotes regenerative response and thus could mitigate neurodegenerative effects.
神经退行性疾病，包括中枢神经系统（CNS）的创伤性损伤和神经退行性疾病，其特征是早期轴突损伤，在成年哺乳动物的中枢神经系统中不会再生，导致永久性神经功能缺损。再生能力丧失的主要原因之一被认为是神经元内在轴突生长能力在发育过程中的下降。许多转录因子参与了轴突再生能力的发育丧失，但 miRNA（microRNAs）的功能，miRNA 也是基因表达的调节剂，在轴突再生长中的作用仍不清楚。在最近被确定在中枢神经系统中具有作用的各种 miRNA 中，miR-17 在早期发育过程中高度表达，成为促进轴突再生的有希望的靶标。在这里，我们使用腺相关病毒（AAV）载体在原代皮质神经元中过表达 miR-17（AAV.miR-17），并评估其对体外神经突和轴突再生的影响。虽然 AAV.miR-17 对神经突生长和分支没有显著影响，但它显著增强了划痕损伤后神经突再生和微流控室培养的神经元轴突切断后轴突再生。靶预测和功能注释分析表明，miR-17 调节与自噬和细胞代谢相关的基因表达。我们的研究结果表明，miR-17 促进了再生反应，从而可以减轻神经退行性效应。
