Kinoshita Chisato, Okamoto Yayoi, Aoyama Koji, Nakaki Toshio
Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan;
Teikyo University Support Center for Women Physicians and Researchers, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
Clocks Sleep. 2020 Jul 23;2(3):282-307. doi: 10.3390/clockssleep2030022. eCollection 2020 Sep.
Circadian rhythms are endogenous 24-h oscillators that regulate the sleep/wake cycles and the timing of biological systems to optimize physiology and behavior for the environmental day/night cycles. The systems are basically generated by transcription-translation feedback loops combined with post-transcriptional and post-translational modification. Recently, evidence is emerging that additional non-coding RNA-based mechanisms are also required to maintain proper clock function. MicroRNA is an especially important factor that plays critical roles in regulating circadian rhythm as well as many other physiological functions. Circadian misalignment not only disturbs the sleep/wake cycle and rhythmic physiological activity but also contributes to the development of various diseases, such as sleep disorders and neurodegenerative diseases. The patient with neurodegenerative diseases often experiences profound disruptions in their circadian rhythms and/or sleep/wake cycles. In addition, a growing body of recent evidence implicates sleep disorders as an early symptom of neurodegenerative diseases, and also suggests that abnormalities in the circadian system lead to the onset and expression of neurodegenerative diseases. The genetic mutations which cause the pathogenesis of familial neurodegenerative diseases have been well studied; however, with the exception of Huntington's disease, the majority of neurodegenerative diseases are sporadic. Interestingly, the dysfunction of microRNA is increasingly recognized as a cause of sporadic neurodegenerative diseases through the deregulated genes related to the pathogenesis of neurodegenerative disease, some of which are the causative genes of familial neurodegenerative diseases. Here we review the interplay of circadian rhythm disruption, sleep disorders and neurodegenerative disease, and its relation to microRNA, a key regulator of cellular processes.
昼夜节律是内源性的24小时振荡器，它调节睡眠/觉醒周期以及生物系统的时间安排，以优化生理机能和行为，使其适应环境的昼夜循环。这些系统基本上是由转录-翻译反馈环结合转录后和翻译后修饰产生的。最近，越来越多的证据表明，还需要额外的基于非编码RNA的机制来维持正常的生物钟功能。微小RNA是一个特别重要的因素，在调节昼夜节律以及许多其他生理功能中起着关键作用。昼夜节律失调不仅会扰乱睡眠/觉醒周期和有节律的生理活动，还会导致各种疾病的发生，如睡眠障碍和神经退行性疾病。患有神经退行性疾病的患者通常会经历其昼夜节律和/或睡眠/觉醒周期的严重紊乱。此外，最近越来越多的证据表明睡眠障碍是神经退行性疾病的早期症状，并且还表明昼夜节律系统的异常会导致神经退行性疾病的发生和表现。导致家族性神经退行性疾病发病机制的基因突变已经得到了充分研究；然而，除了亨廷顿舞蹈症外，大多数神经退行性疾病都是散发性的。有趣的是，通过与神经退行性疾病发病机制相关的基因失调，微小RNA的功能障碍越来越被认为是散发性神经退行性疾病的一个原因，其中一些基因是家族性神经退行性疾病的致病基因。在这里，我们综述了昼夜节律紊乱、睡眠障碍和神经退行性疾病之间的相互作用，以及它们与微小RNA（细胞过程的关键调节因子）的关系。
