Cogswell John P, Ward James, Taylor Ian A, Waters Michelle, Shi Yunling, Cannon Brian, Kelnar Kevin, Kemppainen Jon, Brown David, Chen Caifu, Prinjha Rab K, Richardson Jill C, Saunders Ann M, Roses Allen D, Richards Cynthia A
Department of Pharmacogenetics, GlaxoSmithKline Inc., Research Triangle Park, NC 27709, USA.
J Alzheimers Dis. 2008 May;14(1):27-41. doi: 10.3233/jad-2008-14103.
MicroRNAs have essential functional roles in brain development and neuronal specification but their roles in neurodegenerative diseases such as Alzheimer's disease (AD) is unknown. Using a sensitive qRT-PCR platform we identified regional and stage-specific deregulation of miRNA expression in AD patient brains. We used experimental validation in addition to literature to reveal how the deregulated brain microRNAs are biomarkers for known and novel pathways in AD pathogenesis related to amyloid processing, neurogenesis, insulin resistance, and innate immunity. We additionally recovered miRNAs from cerebrospinal fluid and discovered AD-specific miRNA changes consistent with their role as potential biomarkers of disease.
微小RNA在大脑发育和神经元特化过程中发挥着重要的功能作用，但其在诸如阿尔茨海默病（AD）等神经退行性疾病中的作用尚不清楚。利用灵敏的定量逆转录聚合酶链反应（qRT-PCR）平台，我们在AD患者大脑中鉴定出了微小RNA表达的区域和阶段特异性失调。除了文献研究外，我们还通过实验验证揭示了失调的脑微小RNA如何作为AD发病机制中与淀粉样蛋白加工、神经发生、胰岛素抵抗和先天免疫相关的已知和新通路的生物标志物。我们还从脑脊液中回收了微小RNA，并发现了与它们作为疾病潜在生物标志物的作用相一致的AD特异性微小RNA变化。
