Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei, 11529, Taiwan.
Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Biomed Sci. 2020 Apr 7;27(1):49. doi: 10.1186/s12929-020-00636-z.
Recent transcriptome analyses have revealed that noncoding RNAs (ncRNAs) are broadly expressed in mammalian cells and abundant in the CNS, with tissue and cell type-specific expression patterns. Moreover, ncRNAs have been found to intricately and dynamically regulate various signaling pathways in neurodegeneration. As such, some antisense transcripts and microRNAs are known to directly affect neurodegeneration in disease contexts. The functions of ncRNAs in pathogenesis are unique for each disorder, as are the pertinent networks of ncRNA/miRNA/mRNA that mediate these functions. Thus, further understanding of ncRNA biogenesis and effects might aid the discovery of diagnostic biomarkers or development of effective therapeutics for neurodegenerative disorders. Here, we review the ncRNAs that have so far been identified in major neurodegenerative disease etiology and the mechanisms that link ncRNAs with disease-specific phenotypes, such as HTT aggregation in HD, α-synuclein in PD, and Aβ plaques and hyperphosphorylated Tau in AD. We also summarize the known lncRNA/miRNA/mRNA networks that participate in neurodegenerative diseases, and we discuss ncRNA-related treatments shown to delay disease onset and prolong lifespan in rodent models.
最近的转录组分析表明，非编码 RNA（ncRNA）在哺乳动物细胞中广泛表达，在中枢神经系统中含量丰富，具有组织和细胞类型特异性的表达模式。此外，已经发现 ncRNA 可以错综复杂地动态调节神经退行性变中的各种信号通路。因此，一些反义转录本和 microRNA 已知可直接影响疾病情况下的神经退行性变。ncRNA 在发病机制中的功能因每种疾病而异，介导这些功能的 ncRNA/miRNA/mRNA 相关网络也因疾病而异。因此，进一步了解 ncRNA 的生物发生和作用可能有助于发现神经退行性疾病的诊断生物标志物或开发有效的治疗方法。在这里，我们综述了迄今为止在主要神经退行性疾病病因中发现的 ncRNA ，以及将 ncRNA 与疾病特异性表型联系起来的机制，例如在 HD 中 HTT 聚集、在 PD 中 α-突触核蛋白、以及在 AD 中 Aβ斑块和过度磷酸化 Tau。我们还总结了已知参与神经退行性疾病的 lncRNA/miRNA/mRNA 网络，并讨论了显示可延迟疾病发作和延长啮齿动物模型寿命的与 ncRNA 相关的治疗方法。
