Technology for Gene Therapy Laboratory, Central Institute of Sciences, FAV, University of Brasilia, Brasília 70910-900, Brazil.
Neuroprosthetics and Visual Rehabilitation Research Unit, Bioengineering Institute, Miguel Hernández University, 03202 Alicante, Spain.
Cells. 2020 Mar 31;9(4):841. doi: 10.3390/cells9040841.
MicroRNAs (miRNAs) are small double-stranded RNAs that exert a fine-tuning sequence-specific regulation of cell transcriptome. While one unique miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by various miRNAs that bind to complementary sequences at 3'-untranslated regions for triggering the mechanism of RNA interference. Unfortunately, dysregulated miRNAs play critical roles in many disorders, including Parkinson's disease (PD), the second most prevalent neurodegenerative disease in the world. Treatment of this slowly, progressive, and yet incurable pathology challenges neurologists. In addition to L-DOPA that restores dopaminergic transmission and ameliorate motor signs (i.e., bradykinesia, rigidity, tremors), patients commonly receive medication for mood disorders and autonomic dysfunctions. However, the effectiveness of L-DOPA declines over time, and the L-DOPA-induced dyskinesias commonly appear and become highly disabling. The discovery of more effective therapies capable of slowing disease progression -a neuroprotective agent-remains a critical need in PD. The present review focus on miRNAs as promising drug targets for PD, examining their role in underlying mechanisms of the disease, the strategies for controlling aberrant expressions, and, finally, the current technologies for translating these small molecules from bench to clinics.
微小 RNA（miRNA）是一种小的双链 RNA，可对细胞转录组进行微调、序列特异性调节。虽然一个独特的 miRNA 可以调节数百个 mRNA，但每个 mRNA 分子通常都受到各种 miRNA 的调节，这些 miRNA 可以结合到 3'-非翻译区的互补序列上，触发 RNA 干扰机制。不幸的是，失调的 miRNA 在许多疾病中起着关键作用，包括帕金森病（PD），这是世界上第二常见的神经退行性疾病。这种缓慢进展且无法治愈的病理学的治疗对神经科医生构成了挑战。除了恢复多巴胺能传递并改善运动症状（即运动迟缓、僵硬、震颤）的左旋多巴外，患者通常还接受用于治疗情绪障碍和自主功能障碍的药物。然而，随着时间的推移，左旋多巴的有效性会下降，而左旋多巴诱导的运动障碍通常会出现并变得高度致残。发现更有效的能够减缓疾病进展的疗法——神经保护剂——仍然是 PD 的一个关键需求。本综述重点关注 miRNA 作为 PD 的有前途的药物靶点，研究它们在疾病潜在机制中的作用、控制异常表达的策略，以及最后，将这些小分子从实验室转化为临床的当前技术。
