Tan Lin, Yu Jin-Tai, Tan Lan
College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
Mol Neurobiol. 2015;51(3):1249-62. doi: 10.1007/s12035-014-8803-9. Epub 2014 Jun 29.
Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), originate from a loss of neurons in the central nervous system (CNS) and are severely debilitating. The incidence of neurodegenerative diseases increases with age, and they are expected to become more common due to extended life expectancy. Because of no clear mechanisms, these diseases have become a major challenge in neurobiology. It is well recognized that these disorders become the culmination of many different genetic and environmental influences. Prior studies have shown that microRNAs (miRNAs) are pathologically altered during the inexorable course of some neurodegenerative diseases, suggesting that miRNAs may be the contributing factor in neurodegeneration. Here, we review what is known about the involvement of miRNAs in the pathogenesis of neurodegenerative diseases. The biogenesis of miRNAs and various functions of miRNAs that act as the chief regulators will be discussed. We focus in particular on dysregulation of miRNAs which leads to several neurodegenerative diseases from three aspects: miRNA-generating disorders, miRNA-targeting genes and epigenetic alterations. Furthermore, recent evidences have shown that circulating miRNA expression levels are changed in patients with neurodegenerative diseases. Circulating miRNA expression levels are reported in patients in order to evaluate their application as biomarkers of these diseases. A discussion is included with a potential diagnostic biomarker and the possible future direction in exploring the nexus between miRNAs and various neurodegenerative diseases.
神经退行性疾病，包括阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）和肌萎缩侧索硬化症（ALS），起源于中枢神经系统（CNS）中神经元的丧失，并且严重损害身体机能。神经退行性疾病的发病率随年龄增长而增加，由于预期寿命延长，预计它们会变得更加常见。由于没有明确的机制，这些疾病已成为神经生物学中的一项重大挑战。人们普遍认识到，这些疾病是许多不同遗传和环境影响的最终结果。先前的研究表明，在某些神经退行性疾病的无情发展过程中，微小RNA（miRNA）发生了病理性改变，这表明miRNA可能是神经退行性变的促成因素。在这里，我们综述了关于miRNA参与神经退行性疾病发病机制的已知情况。将讨论miRNA的生物合成以及作为主要调节因子的miRNA的各种功能。我们特别关注导致几种神经退行性疾病的miRNA失调，从三个方面进行阐述：miRNA生成紊乱、miRNA靶向基因和表观遗传改变。此外，最近的证据表明，神经退行性疾病患者的循环miRNA表达水平发生了变化。报告了患者的循环miRNA表达水平，以评估其作为这些疾病生物标志物的应用。还讨论了潜在的诊断生物标志物以及探索miRNA与各种神经退行性疾病之间联系的可能未来方向。
