Pereira Fernandes Diana, Bitar Mainá, Jacobs Frank M J, Barry Guy
University of Amsterdam, Swammerdam Institute for Life Sciences (SILS), 1098XH Amsterdam, The Netherlands.
QIMR Berghofer Medical Research Institute, Herston, QLD, Brisbane, Australia.
Noncoding RNA. 2018 Apr 18;4(2):12. doi: 10.3390/ncrna4020012.
The expansion of long non-coding RNAs (lncRNAs) in organismal genomes has been associated with the emergence of sophisticated regulatory networks that may have contributed to more complex neuronal processes, such as higher-order cognition. In line with the important roles of lncRNAs in the normal functioning of the human brain, dysregulation of lncRNA expression has been implicated in aging and age-related neurodegenerative disorders. In this paper, we discuss the function and expression of known neuronal-associated lncRNAs, their impact on epigenetic changes, the contribution of transposable elements to lncRNA expression, and the implication of lncRNAs in maintaining the 3D nuclear architecture in neurons. Moreover, we discuss how the complex molecular processes that are orchestrated by lncRNAs in the aged brain may contribute to neuronal pathogenesis by promoting protein aggregation and neurodegeneration. Finally, this review explores the possibility that age-related disturbances of lncRNA expression change the genomic and epigenetic regulatory landscape of neurons, which may affect neuronal processes such as neurogenesis and synaptic plasticity.
生物体基因组中长链非编码RNA（lncRNA）的扩增与复杂调控网络的出现有关，这些调控网络可能有助于更复杂的神经元过程，如高阶认知。与lncRNA在人类大脑正常功能中的重要作用一致，lncRNA表达失调与衰老和年龄相关的神经退行性疾病有关。在本文中，我们讨论了已知的神经元相关lncRNA的功能和表达、它们对表观遗传变化的影响、转座元件对lncRNA表达的贡献，以及lncRNA在维持神经元三维核结构中的作用。此外，我们还讨论了lncRNA在衰老大脑中协调的复杂分子过程如何通过促进蛋白质聚集和神经退行性变导致神经元发病机制。最后，本综述探讨了与年龄相关的lncRNA表达紊乱改变神经元基因组和表观遗传调控格局的可能性，这可能会影响神经发生和突触可塑性等神经元过程。
