Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Pharmacol Ther. 2012 Feb;133(2):142-50. doi: 10.1016/j.pharmthera.2011.10.002. Epub 2011 Oct 8.
MicroRNAs (miRNAs) are abundant, endogenous, short, noncoding RNAs that act as important post-transcriptional regulators of gene expression by base-pairing with their target mRNA. During the last decade, substantial knowledge has accumulated regarding the biogenesis of miRNAs, their molecular mechanisms and functional roles in a variety of cellular contexts. Altered expression of certain miRNA molecules in the brains of patients with neurodegenerative diseases such as Alzheimer and Parkinson suggests that miRNAs could have a crucial regulatory role in these disorders. Polymorphisms in miRNA target sites may also constitute an important determinant of disease risk. Additionally, emerging evidence points to specific miRNAs targeting and regulating the expression of particular proteins that are key to disease pathogenesis. Considering that the amount of these proteins in susceptible neuronal populations appears to be critical to neurodegeneration, miRNA-mediated regulation represents a new target of significant therapeutic prospects. In this review, the implications of miRNAs in several neurodegenerative disorders and their potential as therapeutic interventions are discussed.
微小 RNA（miRNAs）是丰富的、内源性的、短的、非编码 RNA，通过与靶 mRNA 碱基配对，作为基因表达的重要转录后调节剂。在过去的十年中，人们积累了大量关于 miRNAs 的生物发生、分子机制及其在各种细胞环境中的功能作用的知识。在阿尔茨海默病和帕金森病等神经退行性疾病患者的大脑中，某些 miRNA 分子的表达发生改变，这表明 miRNA 可能在这些疾病中具有关键的调节作用。miRNA 靶位点的多态性也可能是疾病风险的重要决定因素。此外，新出现的证据表明，特定的 miRNA 可以靶向和调节特定蛋白质的表达，这些蛋白质是疾病发病机制的关键。鉴于易感神经元群体中这些蛋白质的含量似乎对神经退行性变至关重要，miRNA 介导的调节代表了一个具有重要治疗前景的新靶点。本文讨论了 miRNAs 在几种神经退行性疾病中的作用及其作为治疗干预的潜力。
