Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Cell Cycle. 2010 May;9(9):1717-21. doi: 10.4161/cc.9.9.11296. Epub 2010 May 25.
MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs regulating eukaryotic gene expression at the post-transcriptional level. During the last decade, considerable advances have been made in our understanding the biogenesis of miRNAs, the molecular mechanisms by which they regulate gene expression and their functional role in various physiological situations. miRNAs are abundant in the brain where they have crucial roles in development and synaptic plasticity. Accumulating evidence from postmortem brain analyses and animal model studies has begun to suggest that miRNA dysfunction contributes to neurodegenerative disorders. Here, we discuss several examples of investigations demonstrating the role of miRNAs in neurodegenerative disorders. As the expression of disease-causing genes is regulated by certain miRNA(s), changes in these miRNAs could lead to the accumulation of disease-causing proteins, and subsequently to neuronal dysfunction and death. Detailed understanding of these mechanisms can provide potential new therapeutic approaches to slow down or halt the progression of neurodegenerative diseases.
MicroRNAs (miRNAs) 是内源性的、小的、非编码 RNA，在转录后水平调节真核生物基因表达。在过去的十年中，我们在 miRNA 的生物发生、它们调节基因表达的分子机制以及它们在各种生理情况下的功能作用方面取得了相当大的进展。miRNAs 在大脑中含量丰富，在大脑发育和突触可塑性中发挥着关键作用。来自脑尸检分析和动物模型研究的越来越多的证据开始表明，miRNA 功能障碍导致神经退行性疾病。在这里，我们讨论了几个证明 miRNA 在神经退行性疾病中的作用的研究示例。由于致病基因的表达受某些 miRNA 的调节，这些 miRNA 的变化可能导致致病蛋白的积累，进而导致神经元功能障碍和死亡。对这些机制的详细了解可以为减缓或阻止神经退行性疾病的进展提供潜在的新治疗方法。
