Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Via Fratelli Cervi 93, 20090 Segrate, Italy.
Int J Mol Sci. 2020 Apr 25;21(9):3030. doi: 10.3390/ijms21093030.
Psychiatric disorders represent a heterogeneous class of multifactorial mental diseases whose origin entails a pathogenic integration of genetic and environmental influences. Incidence of these pathologies is dangerously high, as more than 20% of the Western population is affected. Despite the diverse origins of specific molecular dysfunctions, these pathologies entail disruption of fine synaptic regulation, which is fundamental to behavioral adaptation to the environment. The synapses, as functional units of cognition, represent major evolutionary targets. Consistently, fine synaptic tuning occurs at several levels, involving a novel class of molecular regulators known as long non-coding RNAs (lncRNAs). Non-coding RNAs operate mainly in mammals as epigenetic modifiers and enhancers of proteome diversity. The prominent evolutionary expansion of the gene number of lncRNAs in mammals, particularly in primates and humans, and their preferential neuronal expression does represent a driving force that enhanced the layering of synaptic control mechanisms. In the last few years, remarkable alterations of the expression of lncRNAs have been reported in psychiatric conditions such as schizophrenia, autism, and depression, suggesting unprecedented mechanistic insights into disruption of fine synaptic tuning underlying severe behavioral manifestations of psychosis. In this review, we integrate literature data from rodent pathological models and human evidence that proposes the biology of lncRNAs as a promising field of neuropsychiatric investigation.
精神障碍是一类具有多种病因的精神疾病，其起源涉及遗传和环境因素的致病整合。这些疾病的发病率非常高，超过 20%的西方人口受到影响。尽管特定分子功能障碍的起源多种多样，但这些疾病会导致精细的突触调节紊乱，而这是行为适应环境的基础。作为认知的功能单位，突触是主要的进化靶标。一致地，精细的突触调节发生在几个层面上，涉及一类新的分子调节剂，称为长非编码 RNA（lncRNA）。非编码 RNA 主要在哺乳动物中作为表观遗传修饰因子和蛋白质组多样性的增强子起作用。lncRNA 的基因数量在哺乳动物中，特别是在灵长类动物和人类中显著扩张，以及它们优先在神经元中的表达，确实代表了一种推动力，增强了突触控制机制的分层。在过去的几年中，已经报道了精神障碍（如精神分裂症、自闭症和抑郁症）中 lncRNA 表达的显著改变，这表明人们对精神疾病严重行为表现背后的精细突触调节紊乱的机制有了前所未有的深入了解。在这篇综述中，我们整合了来自啮齿动物病理模型和人类证据的文献数据，提出 lncRNA 的生物学是神经精神疾病研究的一个有前途的领域。
